Clinical Trials Resource Center

Acute Pain

May 15, 2017

Recro Pharma reported results of a phase III study of intravenous (IV) meloxicam (30mg bolus injection) following major surgery. The multicenter, randomized, double-blind, placebo-controlled trial included patients who had undergone major elective surgical procedures that were expected to result in hospitalization for at least 24 to 48 hours. Major surgical procedures included total hip and knee replacements, spinal, GI, hernia repair and gynecologic surgeries, as well as a range of other surgeries. Patient demographics were balanced across treatment groups and included 40% male patients and about 23% of patients who were over age 65. Unlike the pivotal efficacy trials, minimum pain scores were not required for treatment. Sites were permitted to use opioids and other pain management modes according to their standard of care and meloxicam or placebo was added to this regimen. Patients were randomized in a 3:1 ratio to receive either IV meloxicam 30mg or IV placebo daily for up to seven doses. A total of 721 patients received at least one dose of study medication. In patients age 65 and over, the percentage of patients reporting at least one AE was approximately 7% less in the IV meloxicam 30mg treatment arm compared to the placebo arm. The total occurrence of patients with at least one serious adverse event (SAE) was observed to be lower in the IV meloxicam 30mg group, 2.6%, (14/538 meloxicam patients) than in the placebo group, 5.5%, (10/183 placebo patients). In this safety study, only two SAE events were listed as possibly related to study treatment. Both of these SAEs occurred in one placebo treated patient. No deaths were reported in either treatment group. Approximately 3% of patients in each study group discontinued. Recro Pharma believes the results of this 722 patient phase III safety study support the safety profile of IV meloxicam 30mg and completes the last clinical requirement of the full efficacy and safety program for a New Drug Application (NDA) with the FDA for IV meloxicam 30mg as a novel, non-opioid for management of moderate to severe pain.

December 12, 2016

Recro Pharma reported results of a phase III trial of intravenous (IV) meloxicam for the treatment of acute postoperative pain. In the multicenter, randomized, double-blind, placebo-controlled clinical trial, 219 patients were enrolled and randomly assigned to receive a postoperative regimen of IV meloxicam (30mg bolus injection) or placebo in a 1:1 ratio, once every 24 hours. The IV meloxicam treatment arm demonstrated a statistically significant reduction in SPID24 (p=0.0145) compared to the placebo arm. The study also achieved statistical significance for 10 of the secondary endpoints, including statistically significant differences in SPID12 (p=0.0434), time to perceptible pain relief (p=0.0050), subjects with =30% improvement at 24 hours (p=0.0178), number of times patients required rescue in the first 24 hours after randomization (p=0.0275), as well as number of times rescued from 24 to 48 hours (p=0.0009), and several other pain relief metrics, compared to placebo. The safety results demonstrated that IV meloxicam was well-tolerated, with no difference in serious adverse events (SAEs) related to bleeding for IV meloxicam treated patients versus placebo (1 each). The company believes this completes the efficacy program for the IV meloxicam New Drug Application (NDA).

November 28, 2016

Ocular Therapeutix reported results of a phase III trial of Dextenza (dexamethasone insert) 0.4mg for the treatment of post-surgical ocular inflammation and pain. This prospective, multicenter, 1:1 randomized, parallel-arm, double-masked, vehicle-controlled study enrolled 438 patients who were undergoing clear corneal cataract surgery at 21 sites throughout the U.S. The trial successfully met its two primary efficacy endpoints for inflammation and pain, achieving statistically significant differences between the treatment group and the placebo group for the absence of inflammatory cells on day 14 and the absence of pain on day eight, respectively. Fifty-two point three percent of patients treated with Dextenza showed an absence of inflammatory cells in the anterior chamber of the study eye on day 14, compared to 31.1% of those receiving the placebo vehicle control punctum plug (p<0.0001). Seventy-nine point six percent of patients treated with Dextenza reported absence of pain in the study eye on day eight, compared to 61.3% of those receiving the placebo vehicle control punctum plug (p<0.0001). Ocular Therapeutix has submitted an NDA to the FDA. 

September 6, 2016

Heron Therapeutics issued results of a phase II study of HTX-011 for the management of post-operative pain in patients undergoing inguinal hernia repair. Study 202 was a randomized, placebo-controlled, double-blind, phase II clinical study that evaluated HTX-011 at two doses (200mg and 400mg) compared to placebo. There was a 29% reduction in pain as measured by first 24 hours post-surgery (SPI 0-24) (p=0.008). HTX-011 by instillation (28.4% reduction in SPI 0-24) was equally as effective as HTX-011 by injection (29.2% reduction in SPI 0-24). The pain reduction was long-lasting, with a statistically significant, 25% reduction through 48 hours (SPI 0-48; p=0.038). Mean time to first opioid rescue medication was 110% longer (13.3 hours versus 27.9 hours). Mean total opioid consumption was 36% less through 96 hours post-surgery. The number of patients that did not take any opioid rescue medication at all through 96 hours post-surgery was approximately double (21% versus 11%). The company plans to initiate a phase III program.

August 22, 2016

AcelRx Pharmaceuticals reported results of the phase III trial SAP302 of ARX- 04 (sufentanil sublingual tablet, 30mcg) in patients who presented to the emergency room with moderate to severe acute pain associated with trauma or injury. The ARX- 04 program is comprised of three studies in patients with moderate-to-severe acute pain: SAP301, a double-blind, placebo-controlled trial in ambulatory abdominal surgery patients; SAP302, an open-label trial in adult emergency room patients; and SAP303, an open-label trial in postoperative patients. SAP302 enrolled patients in two cohorts. The initial phase enrolled 40 adults who were administered a single dose of ARX-04 and an extension phase enrolled 36 adults who were eligible to receive up to four doses of ARX-04, given hourly as needed for pain. Overall, the 76 adults treated with ARX-04 in this study experienced a mean pain intensity difference to baseline of 2.9 from a baseline of 8.1, or 35%, on a zero to 10 numeric rating scale at 60 minutes. Of these 36 patients, seven received a second dose of ARX-04, and two received a third dose. For 75% of patients in the second cohort, a single dose of ARX04 was sufficient for pain relief and only 8% of patients received morphine in addition to ARX-04. Patients reported a mean pain intensity decrease of 1.1 compared to baseline 15 minutes following first administration of ARX-04, and a decrease of 1.9 after 30 minutes. Overall ARX-04 was well-tolerated in this study, with 79% of patients reporting no adverse events.

May 16, 2016

TherapeuticsMD released results of a phase III trial of TX-004HR moderate-to-severe vaginal pain during sexual intercourse (dyspareunia). The randomized, double-blind, placebo-controlled, multicenter, study dosed TX-004HR at 25mcg, 10mcg and 4mcg doses in postmenopausal women with a moderate-to-severe dyspareunia. At week 12, all TX-004HR doses compared with placebo significantly improved the four co-primary endpoints, including vaginal superficial cells, vaginal parabasal cells, vaginal pH and the severity of dyspareunia (all p<0.00001 except dyspareunia at 4mcg p=0.0149). Moreover, the changes in cytology, pH and dyspareunia were significant at all intermediate time points (weeks two, six and eight). The Rejoice Trial secondary endpoint result for vaginal dryness was also statistically significant for all three doses evaluated, as moderate-to-severe vaginal dryness was reported by 93% of patients at baseline, and was significantly improved (p<0.02) for all doses at weeks two, six, eight and 12 (except the 4mcg dose at week two). A post-study patient questionnaire showed TX-004HR had high patient acceptability and satisfaction. TX-004HR was well-tolerated; the most frequently reported treatment-emergent adverse events (AEs) were headache, vaginal discharge, nasopharyngitis and vulvovaginal pruritus. Vaginal discharge and vulvovaginal pruritus were numerically higher in the placebo group. No clinically significant differences in AEs between treatment and placebo groups were observed. TherapeuticsMD plans to use the Rejoice Trial data as the basis for an NDA to the FDA for TX-004HR.

November 23, 2015

AcelRx Pharmaceuticals has released results in a phase III study of Zalviso (sufentanil sublingual tablet system 15mcg) for the treatment of faster onset of pain relief in obese (BMI 30kg/m2) post-surgical patients. Patients who self-administered Zalviso experienced statistically significantly improved pain relief when compared to self-administered IV morphine as measured by pain intensity difference to baseline (PID). Significant differences in PID were observed as early as 45 minutes after the first dose (p<0.05), a trend that continued until six hours after the initial dose (p<0.001), after which time PID scores equilibrated between the two groups. Results of the subgroup analysis presented by AcelRx also show that obese patients who administered Zalviso experienced statistically fewer adverse events than did those receiving intravenous patient-controlled analgesia morphine. While overall adverse event rates were comparable, incidence rates of anemia, leukocytosis (increase in white blood cells), vomiting, hypoalbuminemia (decrease in albumin levels), hyponatremia (decrease in sodium levels), urinary retention and pruritus (itching) were all significantly lower in the Zalviso arm compared to the morphine arm (p≤0.05).

November 9, 2015

Elite Pharmaceuticals has reported results of a phase III trial of opioid abuse-deterrent candidate ELI-200 for the treatment of moderate to severe pain. It was a multicenter, randomized, multiple-dose, double blind, placebo-controlled and parallel group study. The trial randomized 163 patients. The pivotal trial met its primary endpoint (p=0.001), demonstrating statistical significance that the product provided pain relief following surgery in the treatment group using ELI-200 compared to the placebo group. Secondary endpoint results were consistent with primary findings and included safety measures. There were no serious adverse events or deaths related to ELI-200 reported during the conduct of the trial. Elite intends to submit an NDA to the FDA for abuse-deterrent ELI-200 by year-end.

September 14, 2015

Collegium Pharmaceutical reported results of a phase III trial of Xtampza ER (oxycodone extended-release capsules) for moderate-to-severe chronic low back pain. The multicenter, randomized, double-blind, enriched enrollment, randomized withdrawal, placebo-controlled study met its primary endpoint, which showed a statistically significant difference in average pain intensity from Randomization Baseline to week 12 between the Xtampza ER and placebo groups (p<0.0001). All sensitivity analyses of the primary endpoint also were statistically significant. Xtampza ER had an adverse event profile consistent with other opioids, was well-tolerated, and no new safety concerns were identified. The company is seeking FDA approval for Xtampza ER.

August 17, 2015

Adynxx reported results of a phase II trial of AYX1 for acute pain and the prevention of chronic pain following surgery. The 120-subject, multicenter, double-blind, placebo-controlled study followed subjects for 42 days after knee replacement surgery, with patients receiving standard-of-care pain management plus either a single preoperative intrathecal injection of AYX1 or placebo. AYX1 demonstrated a statistically significant difference and clinically meaningful reduction in pain with walking from day seven to 28 compared to placebo, the primary post-discharge endpoint. The treatment effect was sustained through the 42-day study period, highlighting the unique pain-modifying properties of AYX1. AYX1 also demonstrated a statistically significant difference and clinically meaningful reduction in pain at rest from day seven to 28, a key secondary endpoint, similarly maintained through the 42-day study period. Consistent with prior trials, AYX1 had an excellent safety profile and the adverse-event rate observed during the trial was typical for a population undergoing knee replacement. In 2013, the FDA granted Fast Track designation to AYX1 Injection for the prevention of chronic pain. The company intends to initiate phase III trials in 2016.

June 1, 2015

Endo Pharmaceuticals reported results of two phase III studies of buprenorphine HCL buccal film using BioErodible MucoAdhesive (BEMA) drug delivery technology for chronic lower back pain. The studies were both double-blind, randomized, placebo-controlled, enriched-enrollment studies. A total of 971 randomized patients completed both trials, including pain sufferers who either had received opioid therapy (study EN3409-307; abstract 437) or were opioid-naive at the start of the study (study EN3409-308; abstract 439). Overall, average pain scores increased more in the placebo arm v. BEMA buprenorphine at week 12 from baseline, and the difference between the two groups was statistically significant. EN3409-307/opioid experienced population mean score change was 1.92, placebo v. 0.88, BEMA buprenorphine; p<0.00001, and EN3409- 308/opioid naive population mean score change was 1.59, placebo v. 0.94, BEMA buprenorphine; p=0.0012. A statistically significant percentage of patients on BEMA buprenorphine experienced pain reductions of greater than 30% compared to placebo (EN3409-307: 64.2% v. 30.6%; p<0.0001; EN3409-308: 62.7% v. 46.9%; p=0.0012). The drug currently is under review by the FDA with a PDUFA action date in October 2015 for use in patients with pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.

January 26, 2015

Mesoblast has issued positive results of a phase II program of MPC-06-ID for the treatment of chronic low back pain due to degenerative disc disease. In the randomized, placebo-controlled trial of 100 patients, a single injection of Mesoblast’s allogeneic investigational mesenchymal precursor cell (MPC) product, MPC-06-ID, was welltolerated. A single injection of 6 million MPCs induced substantial and sustained pain relief over 24 months. At 12 and 24 months, 46% and 48% of MPC-06-ID-treated patients achieved minimal or no residual pain (VAS less than or equal to 20) compared with 13% and 13% of saline treated patients, p=0.042 and 0.093, respectively. In patients who received a single injection of six or 18 million MPCs, 44% and 42%, respectively, achieved the target composite endpoint of treatment success at both six and 12 months (50% reduction in pain, 15-point improvement in function and no further treatment intervention), compared with 13% of saline controls (p=0.006 and p=020). In patients who received six million MPCs and achieved the target composite endpoint of treatment success at both six and 12 months, 86% (11 of 13) maintained treatment success at 24 months (32% v. 11% saline controls, p=0.001). The phase III program for this indication has been initiated.

December 22, 2014

Trevena released results from its randomized, double-blind, placebo- and active-controlled phase II trial of TRV130 in moderate-to-severe postoperative acute pain. Doses of 2mg and 3mg of TRV130 at three-hour intervals achieved a statistically significant reduction in pain intensity difference from placebo over 48 hours, measured as the time-weighted average change in pain score (TWA0-48). At 2mg, TRV130 reduced average pain score (LS mean change in TWA0-48) by 1.4 points (p=0.0024 v. placebo; all p-values 1-sided). At 3mg, TRV130 reduced LS mean TWA0-48 by 2.4 points (p<0.0001 v. placebo). TRV130 achieved a reduction in mean pain intensity of up to approximately six points, with notable efficacy at five minutes, the first pain intensity assessment after dosing. Over 48 hours, 3mg of TRV130 at three-hour intervals achieved a statistically significant reduction in pain intensity difference from 4mg morphine at four-hour intervals, reducing average pain score (LS mean change in TWA0-48) by one point v. morphine (p=0.014). When study pain was most severe, during the first three hours after the initial dose, TRV130 at 1mg, 2mg and 3mg showed a statistically significant reduction in pain (TWA0-3) v. placebo (LS mean change -1.0, -2.4, and -3 respectively; p=0.021, p<0.0001 and p<0.0001, respectively). More patients reported statistically greater peak pain relief during the first dosing period for 2mg and 3mg TRV130 compared to 4mg morphine (p=0.005 and p<0.0001 for TRV130 2mg and 3mg v. morphine, respectively). A phase III study is planned.

August 18, 2014

Collegium Pharmaceutical issued results of a phase III study of Oxycodone DETERx for the treatment of patients with moderate-to- severe chronic low back pain. The phase III study was a multicenter, double-blind, enriched-enrollment, randomized-withdrawal, placebo-controlled study of Oxycodone DETERx versus placebo in opioid-experienced and opioid-naïve subjects with moderate-to-severe chronic low back pain. Patients who achieved a stable and effective dose of Oxycodone DETERx during the open-label titration phase were randomized (n=389) into the 12-week, double-blind maintenance phase, in which they either were maintained on their current dose regimen of Oxycodone DETERx or were tapered to placebo. The primary efficacy endpoint of the study was the change in average pain intensity from baseline to week 12; pain was measured using an 11-point pain intensity numerical rating scale (PI-NRS). The study met the primary efficacy endpoint, showing patients with chronic low back pain treated with Oxycodone DETERx experienced a statistically significant reduction in pain compared with placebo (p< 0.0001). The company is positioned to file an NDA with the FDA for Oxycodone DETERx by the end of 2014.

June 16, 2014

OptiNose reported results of a trial comparing AVP-825 to sumatriptan tablets for migraine pain during the first 30 minutes after treatment. The multi-center, randomized, double-blind, double-dummy crossover, multi-attack study enrolled 275 migraine sufferers and treated a total of 1,531 acute migraines with either the only dose of AVP-825 (22mg) plus a placebo tablet or with a placebo delivered with an OptiNose Bi-Directional Breath Powered device, plus a high dose (100mg) sumatriptan tablet. The trial showed with AVP-825 treatment, early reduction in pain was achieved in more headaches than with oral sumatriptan. The primary endpoint showed during the first 30 minutes, headache pain intensity was statistically significantly lower with AVP-825 treatment (p<0.0001). In addition, the trial achieved statistical significance for relevant secondary measures of Pain Relief and Pain Freedom as early as 15 minutes and at all of the following early time points measured (30, 45, 60, 90) before 120 minutes. Less than 2% of subjects experienced an adverse event leading to treatment discontinuation with use of either medication and there were no serious adverse events. An NDA for AVP-825 was filed earlier this year, and the Prescription Drug User Fee Act (PDUFA) V goal date is Nov. 26.

May 19, 2014

Iroko Pharmaceuticals released results of a phase III study of TIVORBEX (indomethacin) for post-surgical acute pain. The study included 462 patients, aged 18–68, who were randomized to receive TIVORBEX 40mg three times daily (TID) or twice daily (BID) or 20mg TID, celecoxib (400mg loading dose followed by 200mg BID) or placebo. Patients randomized to the 40mg of TIVORBEX TID and BID treatment arms used an average of 2.7 tablets of opioid containing analgesics; the TIVORBEX 20mg TID group used an average of three tablets, the celecoxib group used an average of 3.1 tablets and patients in the placebo group used an average of five tablets. The time to first use of rescue medication, measured following the start of treatment with either TIVORBEX or placebo, occurred later on average in the TIVORBEX 40mg TID, 40mg BID and celecoxib 200mg twice daily groups compared with placebo. The difference was statistically significant for the TIVORBEX 40mg TID group (P = 0.008) compared to placebo. About half as many opioid-containing tablets were used in the TIVORBEX arms compared to the placebo group over 48 hours. The most common adverse events in this study (>5%) included nausea, dizziness and vomiting, and were generally similar across treatment groups. TIVORBEX recently was approved by the FDA for the treatment of mild to moderate acute pain in adults.

May 5, 2014

Teva Pharmaceutical Industries released result of a phase III study of CEP-33237 (hydrocodone bitartrate) extended-release tablets providing potential abuse-deterrent properties in the treatment of patients’ chronic low back pain as measured by both weekly average Worst Pain Intensity (WPI) and weekly Average Pain Intensity (API) scores. The study utilized a randomized, double-blind, placebo-controlled, randomized- withdrawal design to evaluate the efficacy and safety of an abuse-deterrent formulation of extended-release hydrocodone bitartrate at doses ranging from 30mg to 90mg every 12 hours. All patients (both placebo and active arms) were administered CEP-33237 in an open-label phase to identify the maintenance dose that provided adequate analgesia with acceptable tolerability. Responders then were randomized to receive either placebo or their identified maintenance hydrocodone dose. The trial measured the changes in patients’ weekly average WPI between randomization and week 12 of treatment. After randomization, patients who continued receiving CEP- 33237 maintained their improved WPI score, whereas patients who were randomized to receive placebo had a significant worsening of their WPI compared to baseline (0.07 for CEP-3327 v. 0.71 for placebo, p<0.001). Significant improvement in patients’ pain scores for the weekly API also was achieved (p<0.001) when an analysis was performed in patients randomized to continue receiving CEP-33237 in comparison to those randomized to receive placebo. Teva expects to submit a NDA for CEP-33237 to the FDA by the end of 2014.

March 24, 2014

Purdue Pharma issued results of a phase III trial of hydrocodone bitartrate for the treatment of chronic low back pain. The doubleblind, randomized, multi-center, placebo-controlled, phase III study evaluated 588 opioidnaive and opioid-experienced patients with moderate to severe chronic low back pain over a 12-week, double-blind period. Of the patients who were randomized, the weekly average pain score at study entry was 7.4 on a scale of zero to 10 (0=no pain and 10=pain as bad as you can imagine). To achieve adequate pain control prior to randomization, the dose for hydrocodone bitartrate extended-release was increased once every three to five days, if necessary, until a stabilized once-daily dose was identified (20mg-120mg). The majority of patients treated with hydrocodone bitartrate dosed once daily experienced at least a 30% improvement in pain intensity. Nearly half of patients (48%) achieved a 50% improvement with hydrocodone bitartrate. The most common adverse events (5%) reported by patients treated with the once-daily agent were constipation, nausea, vomiting, dizziness and headache. The company plans to file an NDA with the FDA later in 2014 requesting approval to market the medication.

March 10, 2014

Pacira Pharmaceuticals issued results of phase III trials of EXPAREL (bupivacaine liposome injectable suspension) in femoral nerve block for total knee arthroplasty. The pivotal phase III trial evaluated 183 patients who were randomized to receive either 266mg of EXPAREL or placebo, with all patients offered rescue narcotics as needed. Results demonstrated statistical significance in favor of EXPAREL for cumulative pain scores over 72 hours as measured by the area under the curve (AUC) (P<0.0001). The preliminary safety analysis was comparable between the two groups. EXPAREL met its primary efficacy endpoint. Regulatory filings will follow.

February 17, 2014

Spinifex Pharmaceuticals has issued results of a phase II trial of EMA401 for the treatment of PHN chronic pain without CNS side effects. The phase II trial met its primary endpoint by showing patients randomized to EMA401 achieved a greater reduction in pain from baseline to the last week of 28 days of treatment than patients randomized to placebo. The mean pain intensity reduction from baseline after four weeks of treatment was: EMA401: -2.29; Placebo: -1.60; p = 0.007. A significantly greater proportion of patients on active treatment reported a more than 30% reduction in mean pain intensity score compared to baseline (i.e. responder rate) (EMA401: 57.6%; Placebo: 35.2%; p = 0.0023), meeting a key secondary endpoint. EMA401 was generally safe and well tolerated with no serious treatment-related adverse events reported.

February 10, 2014

Mesoblast released results of a phase II trial of Mesenchymal Precursor Cells (MPCs) in patients with chronic moderate to severe discogenic low back pain. The trial enrolled 100 patients with moderate to severe low back pain persisting for more than six months and caused by early disc degeneration (less than 30% disc height loss, 83% below Pfirrmann Grade 5 by MRI). Patients were enrolled across 13 sites in the U.S. and Australia and randomized to receive direct intra-disc injection of saline (n=20), hyaluronic acid (HA, n=20), 6 million allogeneic MPCs in hyaluronic acid carrier (6M, n=30) or 18 million allogeneic MPCs in hyaluronic acid carrier (18M, n=30). Patients were evaluated over 36 months for long-term treatment effects. While mean pain scores, as measured by a Visual Analog Scale, were similar for all four groups at baseline (67 points for saline, 72 points for HA, 70 points for 6M MPC, 72 points for 18M MPC), at 12 months MPC treatment resulted in significantly greater pain reduction than was seen in controls. Mean pain reduction at 12 months was 40 points for the 18M MPC group, 37 points for the 6M MPC group, 27 points for HA controls and 27 points for saline controls (p=0.046 and p=0.11, respectively, for 18M MPC and 6M MPC v. pooled controls). Both MPC dose groups had a significantly greater proportion of patients with 50% or more reduction in back pain from baseline compared to the pooled controls (6M, p=0.009, 18M p=0.038). At 12 months, MPC treatment resulted in greater improvement in function than was seen in controls, as measured by the Oswestry Disability Index (ODI). Mean reduction in the ODI functional disability score was 43% for the 18M MPC group, 35% for the 6M MPC group, 30% for HA controls and 28% for saline controls (p=0.09 for 18M MPC group v. saline). Mesoblast plans to meet with regulatory authorities to discuss product registration trials.

February 3, 2014

Endo Pharmaceuticals issued results of a phase III trial of BEMA buprenorphine for the treatment of moderate to severe chronic pain in patients requiring around-the-clock opioid therapy for an extended period of time in both patients who are opioid naive and opioid experienced. The trial was an enriched-enrollment, double-blind, randomized withdrawal study. A total of 462 patients who titrated to a well-tolerated, effective dose were randomized to either continue on that dose of BEMA buprenorphine or receive placebo (BEMA film with no active drug), with treatment continuing for 12 weeks. The trial successfully met its primary efficacy endpoint in demonstrating BEMA buprenorphine resulted in significantly (p<0.005) improved chronic pain relief compared to placebo. Additional secondary endpoints were supportive of the efficacy of BEMA buprenorphine compared to placebo. The most commonly reported adverse events in patients treated with buprenorphine compared to placebo were nausea (10% v. 8%), vomiting (4% v. 2%) and constipation (4% v. 2%). A second phase III clinical study of BEMA buprenorphine in an opioid “experienced” patient group is ongoing.

January 13, 2014

AcelRx Pharmaceuticals issued results of a phase II study of ARX-04, an investigational single-dose sublingual sufentanil NanoTab for moderate-to-severe acute pain. This dose-ranging study randomized 101 patients following bunionectomy surgery in a 2:2:1 ratio to 30mcg sufentanil, 20mcg sufentanil or placebo treatment arms. The intent-to-treat (ITT) population in this study averaged 42.5 years of age and was evenly balanced for males and females (51%:49%). Ninety-one percent of patients entering the study completed the full 12-hour study period. SPID-12 (Summed Pain Intensity Difference to baseline during the 12-hour study period) scores, the primary endpoint, were +6.53 for 30mcg sufentanil-treated patients and -7.12 for placebo-treated patients, the difference between the two groups being highly statistically significant (p=0.003). The 20mcg sufentanil-treated patients did not achieve SPID- 12 scores that differentiated from placebo. For the time-weighted sum of pain relief scores over the 12-hour study period, or TOTPAR12, there was a statistically significant difference in favor of the 30mcg group over placebo (9.73 v. 4.37 p=0.002). Patients treated with the 30mcg dose of sufentanil showed a rapid onset of action with a statistically significant beneficial difference in pain relief (p<0.001) and pain intensity (p<0.01) seen at 30 minutes after dosing compared to placebo. These data will be reviewed in AcelRx’s end-of-phase II meeting with the FDA in order to define the phase III development program for ARX-04, which AcelRx intends to initiate in the second half of 2014.

November 25, 2013

Clinuvel Pharmaceuticals reported results of a phase III study of SCENESSE (afamelanotide 16mg) to patients with erythropoietic protoporphyria (EPP). The six-month, randomized, multicenter, double-blind, placebocontrolled study enrolled 93 adult EPP patients in the U.S. Patients were randomized into two treatment groups and given either SCENESSE or placebo implants every two months. Median total direct sunlight exposure was 64.13 hours (range 0 to 650.5 hours) in the active group compared with 47.5 hours (range 0 to 224 hours) for placebo recipients (p=0.107, Kruskal-Wallis test). The distribution of the number of days with sun exposure of various time intervals (30-minute intervals) was significantly different between the treatment groups (p<0.001, Cochran- Mantel-Haenszel test). SCENESSE recipients reported more days when they had pain-free exposure of 60 minutes or more (the time of greatest risk of burns). The results showed that after receiving their second SCENESSE administration, patients had a significantly higher tolerance to light irradiation on the lower back and back of the hand (median change from baseline in minimum symptom dose on lower back at day 90, 227.5 v. -2.4 J/cm2; p<0.001, Wilcoxon test). The difference in the distribution of days during which pain was experienced was significant between the two treatment groups (p<0.0001, Cochran-Mantel-Haenszel test). The final stage of EMA review of SCENESSE is expected to continue in January 2014.

November 11, 2013

Cara Therapeutics issued results of a phase II trial of I.V. CR845 for the treatment of acute pain. The randomized, doubleblind, placebo-controlled trial of I.V. CR845 (0.005mg/kg/dose) enrolled 51 women and men undergoing a primary unilateral first-metatarsal bunionectomy surgery in the U.S. Repeat dosing of I.V. CR845 over 48 hours post-surgery provided statistically greater pain reduction than placebo at both the 24- and 48-hour time points following initiation of treatment, as assessed using the FDA recommended endpoint, the Summed Pain Intensity Difference (SPID). The I.V. CR845 treatment arm met the trial’s primary endpoint of a statistically significant reduction in pain intensity, as measured by the SPID score, over the initial 24-hour time period (SPID0-24; p<0.05) compared to placebo. The I.V. CR845 treatment arm also met the secondary endpoint of a statistical reduction in pain intensity over the entire 48-hour dosing period (SPID0-48; p<0.025). In addition, I.V. CR845 treatment resulted in a statistically significant reduction in the incidence of opioid-related adverse events of nausea and vomiting (by 60% and 80%, respectively; p<0.05) compared to placebo during the 48-hour treatment period.

November 4, 2013

AstraZeneca released results of a phase III trial of naloxegol for the treatment of non-cancer pain and opioid-induced constipation (OIC). The study enrolled 844 patients, provided a once-daily 25mg dose of naloxegol and lasted 52 weeks, comparing naloxegol (n=534) to usual care (n=270). Usual care was defined as the investigator’s choice of an existing laxative treatment regimen for OIC. Most naloxegol-emergent gastrointestinal adverse events (AEs) occurred early in treatment and were transient with nine patients (1.6%) discontinuing naloxegol due to abdominal pain. Most common treatment-emergent AEs occurring more often with naloxegol v. usual care were abdominal pain (17.8% v. 3.3%), diarrhoea (12.9% v. 5.9%), nausea (9.4% v. 4.1%), headache (9.0% v. 4.8%) and flatulence (6.9% v. 1.1%). Pain scores and opioid doses were comparable between treatment groups and were stable throughout the study. There were two opioid withdrawal AEs reported in patients taking naloxegol (both were deemed unrelated to treatment with naloxegol).

August 12, 2013

Pharmanest released results of a phase II study of SHACT for the treatment of pain in connection with intrauterine device insertion. SHACT is a product based on a formulation of lidocaine, an anesthetic, and a proprietary application device developed to simplify topical application in the cervix and uterus. The randomized, double-blind trial involving 218 women between ages 18 and 45 showed women receiving SHACT during IUD insertion experienced a more than 30% reduction in pain, measured on a visual analogue scale, compared to patients who received placebo. This effect was statistically significant (p < 0.0001). Patients who received SHACT also experienced less discomfort (p < 0.05) than women who received placebo. Women who received SHACT reported similar adverse events, in terms of type and frequency, as women who received placebo treatment.

April 22, 2013

Iroko Pharmaceuticals issued results from a phase III trial of lower dose submicron indomethacin for the treatment of post surgical acute pain. This multi-center, double-blind, placebo- and active- controlled study enrolled 462 patients with moderate to severe pain following bunionectomy surgery. Subjects received 40mg submicron indomethacin three times daily or twice daily, 20mg submicron indomethacin three times daily, 400mg loading dose of celecoxib plus 200mg twice daily, or placebo. Statistically significant overall decreases in pain intensity were demonstrated for 40mg submicron indomethacin three times daily (509.6, p<0.001), 40mg submicron indomethacin twice daily (328.0, p=0.046), 20mg submicron indomethacin three times daily (380.5, p=0.017), compared with placebo (67.8). Although there was some evidence of analgesia for celecoxib (279.4), it did not achieve statistical significance compared with placebo. Some evidence of pain control was observed as early as 30 minutes in the 40mg submicron indomethacin three times daily (2.9) and 40mg submicron indomethacin twice daily (2.6) groups compared with placebo (0.2). The drug was well tolerated. The most frequent adverse events were similar across treatment groups and included nausea, post-procedural edema, dizziness and headache.

January 16, 2012

DURECT issued results from a phase III trial of Posidur, their sustained release formulation of bupivacaine for the treatment of post-surgical pain. This international, multi-center, randomized, double-blind, controlled trial, BESST, enrolled 305 subjects undergoing general abdominal surgical procedures. The subjects were placed in one of three cohorts: Cohort 1: subjects were randomized to either Posidur 5.0 mL or Bupivacaine HCl solution after laparotomy, in cohort 2 subjects were randomized to either Posidur 5.0 mL or Bupivacaine HCl solution after laparoscopic cholecystectomy and in cohort 3 subjects were randomized to either Posidur 5.0 mL or placebo after laparoscopically-assisted colectomy. The co-primary endpoints were pain intensity and the use of opioid analgesics over the first three days (72 hours) following surgery. Although the results trended positive for both endpoints, they did not reach statistical significance. Pooled data from cohorts 1 and 2 showed a mean reduction in pain of approximately 20% (p≡0.0111) for the Posidur group compared to the bupivacaine HCl group and approximately 18% less opioids were consumed for supplemental analgesia compared to the bupivacaine HCl arm (p≡0.5455). In cohort 3 the group treated with Posidur reported a mean reduction in pain of approximately 7% (p≡0.1466) and approximately 16% less opioids were consumed for supplemental analgesia compared to the bupivacaine HCl arm (p≡0.5897).

September 19, 2011

Innocoll issued results from two phase II trials of Xaracoll, their collagen/bupivacaine sponge implant, for the treatment of post-operative pain. Study INN-CB-010 was a randomized, single dose, double-blind, placebo controlled study in 50 men undergoing open laparotomy inguinal herniorrhaphy. Two sponges were implanted during surgery, either placebo or Xaracoll sponges. Study INN-CB-011was a single-dose, open-label study in ten men undergoing laparoscopic inguinal or umbilical herniorrhaphy. The subjects receiving XaraColl demonstrated a statistically significant reduction in the total use of opioid medication through 24 and 48 hours post-surgery as well as a statistically significant increase in the time before rescue opioid medication.

May 2, 2011

Pain Therapeutics reported results from a study of Remoxy, an oral abuse resistant formulation of oxycodone. The double blind, placebo and active-controlled, six-way crossover study enrolled 45 healthy subjects with histories of non-dependent recreational opioid use. The study assessed the abuse potential of Remoxy 40 mg whole and chewed, oxycodone ER 40 mg whole and crushed, oxycodone IR 40 mg crushed and placebo. Treatments were administered in-clinic under various fed/fast conditions that produced the highest bioavailability for each drug. Data are from 32 subjects. The primary endpoint was Drug Liking, as assessed by various pharmacodynamic parameters. Drug Liking was significantly lower for Remoxy 40mg (whole) compared with oxycodone ER 40mg (whole) or oxycodone IR 40 mg (p<0.05). Drug Liking was significantly lower for Remoxy 40mg (chewed) compared with oxycodone ER 40mg (crushed) or oxycodone IR 40 mg (p<0.05). Time to Peak Drug Liking was significantly delayed for Remoxy 40mg (chewed) compared with oxycodone ER 40mg (crushed) or oxycodone IR (p<0.05). Secondary endpoints, including Drug High and Good Effects, chewing duration, taste/texture assessments and safety assessments, were generally the same consistency of effects observed in the primary endpoints. In addition, no subject could chew Remoxy for more than 1.5 minutes despite an allotted time of ten minutes, due to the unpleasant taste/texture.

August 16, 2010

QRxPharma released positive results from a phase II trial of MoxDuo IV for the treatment of moderate to severe postoperative pain following hip replacement surgery. This double blind, active controlled study enrolled 40 subjects at two sites in Germany. Following hip replacement surgery, the subjects were randomized to intravenous MoxDuo (morphine and oxycodone) or morphine alone over a two-part, 48-hour treatment period. The first part consisted of a 65 minute dose-titration in which fixed doses were given once every five minutes until a strong analgesic effect occurred. This was followed by a 47 hour patient controlled analgesia (PCA) period in which patients could self administer a fixed amount of study drug as frequently as once every six minutes. During the initial 65 minute dose-titration period, sum of pain intensity (SPID) scores from baseline were 50% higher among patients in the MoxDuo arm compared to the morphine alone arm. In addition, 67% of subjects receiving MoxDuo reported good to excellent global improvement compared to 53% of those receiving morphine alone. During the entire 48 hour study period, SPID scores were 10% higher among MoxDuo arm compared to the morphine alone arm. PCA data also indicated that subjects in the MoxDuo study arm were able to achieve better pain relief faster and with fewer doses (13 doses versus 17 doses).

December 7, 2009

Pacira released positive results from a phase III trial of Exparel for the reduction of pain in patients undergoing hemorrhoidectomy. This multicenter, randomized, double-blind, parallel-group, active-controlled trial enrolled 189 subjects who received a single administration of either Exparel or placebo. The primary endpoint, a reduction in area under the curve analysis of the numerical rating scale pain score, was reached. Results showed a statistically significant reduction in the Exparel arm compared to placebo through 72 hours (p<0.0001). Multiple secondary endpoints were also reached. The percentage of patients who were opioid free was statistically significantly higher (p<0.0008) in the Exparel group compared to the placebo group. The median time to first opioid rescue between the arms was also statistically significant; one hour for the placebo arm versus 14 hours for the Exparel arm (p<0.0001). In addition, the Exparel treatment group showed a statistically significantly reduced total opioid consumption through 72 hours compared to the placebo group (p≡0.0006).

November 2, 2009

AcelRx reported results from a phase II trial of ARX-03, a sublingual formulation of sufentanil plus triazolam, for the reduction of agitation, anxiety and pain during surgical procedures. This randomized, double-blind, placebo-controlled study enrolled 40 subjects who were undergoing an elective low-volume abdominal liposuction procedure. The subjects were randomized to receive either a single sublingual dose of ARX-03 or placebo prior to the injection of a local anesthetic and the subsequent liposuction procedure. The primary endpoint was efficacy of ARX-03 compared to placebo in providing mild sedation during the procedure, as assessed using the validated, objective Richmond Agitation-Sedation Scale (RASS). The cumulative RASS score over the 4-hour study period was significantly better for the ARX-03 arm than for placebo (p<0.001) and a separation from placebo was seen as early as 30 minutes post-dosing (p≡0.046), indicating a rapid onset of sedation. The efficacy of ARX-03 in reducing anxiety compared to placebo, a key secondary endpoint, was reached with significance. The cumulative anxiety score (patient-reported 11-point scale) over 4 hours was significantly lower for ARX-03 than for placebo (p≡0.004), and a separation from placebo was seen as early as 15 minutes post-dosing (p≡0.034), indicating a rapid onset of anxiolysis. In addition, analgesic efficacy (Summed Pain Intensity) which reflects the cumulative pain score over the 4-hour study period was lower for the group treated with ARX-03 relative to those treated with placebo (median values of 13 versus 23 in the active and placebo groups, respectively; p≡0.09).

August 17, 2009

Omeros reported positive results from a phase I/II trial of OMS302 for the maintenance of mydriasis and the treatment of postoperative pain following cataract surgery. This randomized, double-blind, vehicle-controlled and parallel-assigned study enrolled 60 subjects undergoing age-related cataract extraction with lens replacement. The subjects were placed in one of three treatment arms: in the first arm, OMS302 including both the mydriatic and anti-inflammatory agents was added to a standard irrigation solution used in ophthalmologic surgery and delivered directly to the eye during the operation; in the second arm, subjects received irrigation solution including only the mydriatic agent, and in the third arm, subjects received standard irrigation solution only. The effects of OMS302 on dilation of the pupil during cataract surgery and on pain, discomfort and inflammation following the procedure were analyzed for 14 days. The subjects treated with OMS302 reported less postoperative pain and demonstrated statistically significant improvement in maintenance of mydriasis during the surgical procedure compared to subjects treated with placebo control. There were no serious adverse events and no discontinuations due to adverse events.

July 6, 2009

AcelRx released positive results from a phase II trial of ARX-01 Sufentanil NanoTabs for the treatment of post-operative pain following major abdominal surgery. This randomized, double blind, placebo controlled study enrolled 88 subjects undergoing major abdominal surgery. The subjects were randomized to receive either 10 mcg or 15 mcg doses of ARX-01, or placebo for post-operative pain. ARX-01 was administered sublingually, as needed to treat pain with a minimum re-dosing interval of 20 minutes. The primary outcome was analgesic effect, as measured by pain intensity scores over the 12 hour study period based on SPID-12. Both doses of ARX-01 showed statistically significant reductions in pain intensity over the study period (p<0.001 for each). The proportion of subjects who dropped out due to inadequate analgesia, a clinically meaningful secondary endpoint, was also significantly different from placebo for both treatment groups (p<0.001). ARX-01 was well tolerated.

April 27, 2009

QRxPharma reported positive results from a phase III trial of MoxDuoIR for the treatment of acute moderate to severe pain following bunionectomy surgery. This US-based, double-blind, randomized and repeated fixed-dose study enrolled 179 subjects experiencing moderate to severe pain following a scheduled bunionectomy. When post-operative pain reached a measure of at least 4 (moderate pain) on the Numerical Pain Rating Scale, subjects received either MoxDuoIR, or its individual components, morphine or oxycodone, every 6 hours for 48 hours. The primary endpoint was the achievement of pain relief for MoxDuoIR versus equivalent doses of morphine and oxycodone alone during the first 24 hours following surgery. The analgesic effects of MoxDuoIR (12mg/8mg) were 80%-100% greater than morphine or oxycodone. The MoxDuoIR (6mg/4mg) also showed similar improvements when compared to its individual components. In addition, the frequency of moderate to severe adverse events was 25% to 75% lower among the MoxDuoIR treatment group compared to the individual components. Subjects receiving morphine or oxycodone alone were two to four times more likely to prematurely discontinue dosing than those on MoxDuoIR.

March 23, 2009

Durect reported positive results from a phase IIb trial of Transdur-sufentanil, a transdermal patch formulation of the opioid sufentanil. This open label, two-stage study enrolled 74 opioid-experienced subjects with non-malignant moderate to severe chronic pain. The study was designed to explore the conversion schedule for transitioning this population from current oral and transdermal opioid therapies to Transdur-Sufentanil. Following a baseline screening, the subjects were randomized into multiple titration regimens. After achieving an endpoint of adequate, stable pain control and an acceptable safety profile on Transdur-Sufentanil, they entered a 28-day continuous treatment maintenance period. This was followed by a seven day follow-up period to ensure that an adequate pain control regimen was re-established. Of the 74 initially enrolled subjects, 36 successfully entered the maintenance period. Two acceptable dose titration intervals achieved the desired analgesic effect and side-effect profile. The mean pain score during the maintenance period was 3.88 (on a ratings scale for pain intensity, with 0 being no pain) representing a reduction of approximately 19% from the mean baseline pain score of 4.78. Treatment was safe and well tolerated.

February 16, 2009

Winston Laboratories issued positive results from a phase I trial of the zucapsaicin patch for the treatment of pain. This randomized, double-blind, placebo-controlled study (WL-1001-04-01), enrolled 39 healthy subjects in the US. The subjects received 0.0075% and 0.0150% doses of the patch or placebo for 7 days. The patch was applied once daily to the same area of the abdomen, and worn for 24 hours before replacing with a new patch during the 7 day study duration. The primary endpoint was stinging or burning sensation; secondary endpoints included pharmacokinetics. Data are from 38 evaluable subjects. Both strengths of the Civamide Patch were tolerable when continuously applied to the skin for one week. Transient burning sensations were reported, which progressively lessened or resolved with each new patch application during the study. There was no systemic absorption of civamide detected.

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