December 5, 2016
Braeburn Pharmaceuticals and Camurus issued results of a pivotal, phase III, randomized, double-blind, double-dummy, active controlled trial of weekly and monthly injections of buprenorphine (CAM2038) for treatment of moderate to severe opioid use disorder. In the study, which enrolled 428 patients with opioid use disorder, CAM2038 achieved the main objective of statistical non-inferiority compared to the active comparator of SL BPN/NX for both the FDA and the EMA specified endpoints of responder rate (RR) (CI -3.5%, 10.4%; p<0.001) and percent negative urine samples for opioids (CI -0.2%, 13.7%; p<0.001), respectively. While the study was designed and powered for assessing non-inferiority, the protocol also planned to test superiority against SL BPN/NX based on the pre-defined secondary endpoint of cumulative distribution function (CDF) of the percent urines negative for opioids combined with self-reports for weeks five through 24. The superiority of CAM2038 over SL BPN/NX was established with p=0.004. The retention rate in the trial was approximately 57.5% and, as expected, similar across both treatment arms. The overall safety profiles were comparable between the two treatment groups, with few serious adverse events (SAEs) reported for the CAM2038 and SL BPN/NX (3.2% vs 6%, respectively). There were no reported overdoses in the CAM2038 arm compared to four non-fatal overdoses (three on heroin, one on Klonopin) in the SLBPN/NX arm. Injection site reactions occurred in 19% of the CAM2038 participants vs 22% of the SL BPN/NX participants. Seventy-four percent of the injection site reactions were reported as mild, 26% as moderate, and none were reported as severe. Braeburn and Camurus will work with the FDA and EMA to begin the submission process. The FDA has granted Fast Track designation for CAM2038 subcutaneous injectable products for the treatment of opioid addiction.
August 22, 2016
Indivior released results of a phase III trial
of RBP-6000 buprenorphine monthly depot
for the treatment of opioid use disorder
as part of a complete treatment plan to include
counseling and psychosocial support.
The multicenter, randomized, double-blind,
placebo-controlled study randomized 489
subjects. RBP-6000 achieved the primary
endpoint of the cumulative distribution
function of the percentage of urine samples
negative for opioids combined with
self-reports negative for illicit opioid use
collected from week five through week
24 (p<0.0001 for both dosage regimens v.
placebo). The key secondary endpoint in this
study was treatment success defined as any
subject with 80% of urine samples negative
for opioids combined with self-reports
negative for illicit opioid use from week five
through week 24. The secondary endpoint
was also achieved for both dosage regimens
at p<0.0001 v. placebo. RBP-6000 was
generally well-tolerated in this study. Available
safety findings suggest that 2.8% of
subjects on RBP-6000 experienced a serious
treatment-emergent adverse event (TEAE)
compared with 5.1% of subjects on placebo.
There were no related serious TEAEs across
groups. RBP-6000 has previously received
Fast Track designation from the FDA. Subject
to satisfactory completion of the analysis
and, assuming the FDA review and approval
is achieved within the assumed six month
Priority Review timeline, it is possible that a
marketing authorization could be granted in
Q4 2017 per previous guidance.
June 22, 2015
Titan Pharmaceuticals released results of a phase III, double blind, double dummy clinical study of Probuphine for opioid addiction. The subjects were clinically stable patients receiving maintenance treatment with an approved sublingual dose of buprenorphine/naloxone at a daily dose of 8mg or less for at least three months prior to entering the trial. The study enrolled 177 subjects. Subjects in one group received four Probuphine implants plus daily placebo sublingual tablets, and subjects in the second group received four placebo implants plus daily sublingual buprenorphine/naloxone tablets (8mg/day). There were 177 subjects randomized in the study and 173 subjects were included in the Intent to Treat (ITT) population; 89 in the sublingual buprenorphine/naloxone arm and 84 in the Probuphine arm. Analyses indicate response rates of 96.4% for the Probuphine arm and 87.6% for the sublingual buprenorphine/naloxone arm. The two-sided 95% confidence interval (0.009, 0.167) of the treatment difference (Probuphine—sublingual buprenorphine/naloxone) was well within the pre-defined successful margin for non-inferiority. The overall safety and tolerability profiles for each treatment group were also comparable. Titan and Braeburn intend to resubmit an NDA for Probuphine to the FDA in the second half of this year. The NDA is still considered to be under Priority Review by the FDA.
June 15, 2015
Braeburn Pharmaceuticals released results of a phase III study of Probuphine for the long-term maintenance treatment of opioid addiction. The study enrolled 177 subjects who were randomized to receive either the Probuphine implants or sublingual tablets for six months. Subjects in one group received four Probuphine implants plus daily placebo sublingual tablets. A second group received four placebo implants plus daily sublingual buprenorphine/naloxone tablets (<8mg/day). There were 78 (87.6%) responders in the sublingual buprenorphine/naloxone arm and 81 (96.4%) responders in the Probuphine arm. The number of subjects with no evidence of illicit opioid use for all six months based on urine testing was higher in the Probuphine arm (88%) than the sublingual buprenorphine/naloxone arm (72%) (p=0.008). Braeburn intends to resubmit the NDA for Probuphine to the FDA in the second half of this year. The NDA is under Priority Review by the FDA.
December 15, 2014
Orexo released results of a phase III trial
of Zubsolv compared with Suboxone film
during stabilization of patients with opioid
dependence. The randomized, multicenter,
non-inferiority clinical trial enrolled 758 patients
in the maintenance phase of the study
with either Zubsolv or Suboxone film. At day
15, Zubsolv patients switched to Suboxone
film and those taking Suboxone film switched
to Zubsolv. The co-primary endpoint was
retention in treatment at day 15. On day 15,
the number of patients who were retained
in treatment were similar across the Zubsolv
and Suboxone film arms (74.9% v. 74.4%, respectively,
P=0.866). Despite an average 26%
to 32% percent lower dose of buprenorphine
in Zubsolv compared to that in Suboxone film
used, Zubsolv showed comparable efficacy
to Suboxone film, which may help reduce the
potential for misuse. Zubsolv also demonstrated
no increased rate of withdrawal symptoms
or opioid cravings versus Suboxone film
at day 15 and day 22. The safety profile of
Zubsolv was similar to that of Suboxone film.
March 12, 2012
H Lundbeck released results from three phase III trials of nalmefene for the treatment of alcohol dependence. The trials enrolled 1,997 subjects. The first two placebo-controlled studies (ESENSE1 and ESENSE2) assessed the efficacy of 20 mg doses of nalmefene on excessive alcohol consumption and on the overall alcohol intake per month evaluated over six months. In the third study (SENSE), subjects were treated for 12 months to confirm the drug was well tolerated. The primary goal of ESENSE 1 and ESENSE 2 was to evaluate the efficacy of as-needed use of Selincro versus placebo in reducing the number of heavy drinking days (HDD) and the monthly total alcohol consumption (TAC) over a period of six months. The primary objective of SENSE was to evaluate the long-term safety and tolerability of Selincro over a period of 52 weeks, as well as the efficacy versus placebo at six months. In ESENSE 1 and ESENSE 2, Selincro was superior to placebo in reducing the number of HDDs (p<0.05 in both studies) and TAC (ESENSE 1, p<0.05; ESENSE 2, p≡0.088) at month six. In SENSE, Selincro was more efficacious than placebo (p<0.05) in reducing the number of HDDs and TAC at the majority of the time points and at the end of the study, although not at month six. Selincro was generally well tolerated over 52 weeks. The most frequent adverse events included dizziness, insomnia and nausea.
June 20, 2011
Biotie and H. Lundbeck reported initial results from three phase III trials of nalmefene for the treatment of alcohol dependence. The trials enrolled approximately 2,000 subjects. The first two studies (ESENSE1 and ESENSE2) assessed the efficacy of 20 mg doses of nalmefene on excessive alcohol consumption and on the overall alcohol intake per month in a treatment cycle of 24 weeks. In the third study, SENSE, the subjects were treated for 12 months to confirm drug safety and tolerability. In ESENSE1 and -2 all assessments were consistently in favor of nalmefene compared to placebo. Overall, nalmefene reduced heavy drinking days and total alcohol consumption by more than 50% compared to pre-treatment baseline. The effect was observed already during the first month of treatment and was maintained throughout the study period in the three trials. SENSE confirmed the safety, tolerability and efficacy. The most common adverse events were dizziness, insomnia and nausea and the treatment effect of nalmefene was maintained and improved after one year of treatment.
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.
November 23, 2009
Alkermes reported positive results from a phase III trial of XR-NTX for the treatment of opioid dependence. This randomized, multi-center study enrolled 250 subjects who were dependent on opioids and who had recently been detoxified and abstinent from opioids for a minimum of seven days prior to treatment initiation. The subjects received once-monthly intramuscular injections of either XR-NTX or placebo in combination with counseling for six months. The primary efficacy endpoint was the response profile based on the rate of urine drug screens that were free of opioids during the last 20 weeks of the 24-week double-blind treatment period. Once-monthly XR-NTX demonstrated statistically significant higher rates of clean (opioid-free) urine screens, compared to placebo treatment, as measured by the cumulative distribution of clean urine screens (p<0.0002). All secondary efficacy endpoints were also reached. Data from the intent-to-treat analysis show that the median patient taking XR-NTX had 90% opioid-free urine screens during the evaluation phase of the study. Treatment with XR-NTX also resulted in a significant reduction in opioid craving compared to placebo. XR-NTX was generally well tolerated.
December 11, 2006
Somaxon reported negative results from a phase II/III trial of nalmefene for the treatment of pathological gambling. This randomized, double-blind, placebo-controlled, outpatient, multi-center trial enrolled 225 subjects, diagnosed as pathological gamblers, who received oral nalmefene (20 mg or 40 mg) or placebo. The primary endpoint, mean PG-YBOCS (Yale Brown Obsessive Compulsive Scale modified for Pathological Gambling) as measured at week twelve, was not met. Statistical significance was not seen between either of the treatment groups when compared to placebo. In addition, secondary endpoints were not reached in either dose group and elevation in liver enzymes was observed in some of the nalmefene-treated subjects. Somaxon plans to further assess this data and data from a phase II trial in order to determine a future course of action for nalmefene.
December 4, 2006
Pain Therapeutics reported positive results from a phase I trial of PTI-202, an abuse- resistant opioid painkiller. The trial was designed to assess the safety, tolerability, pharmacokinetic and pharmacodynamic profiles of a single, oral dose of PTI-202 in healthy subjects. Results revealed treatment to be safe and well tolerated, with no adverse events reported. Its release profile appears to be well-suited to use with a chronic pain population. Based on these results, Pain Therapeutics plans to move development of PTI-202 into phase II trials.
August 22, 2005
WEX Pharmaceuticals has announced results of a phase IIa trial of Tetrodin (tetrodotoxin), for the treatment of withdrawal symptoms associated with opioid dependence. Results from the study indicated that a 4-day pre-treatment regimen of the drug failed to attenuate withdrawal symptoms produced by administering naltrexone (an opioid receptor blocker) to methadone-maintained subjects. Safety results yielded a positive overall profile, and there was no indication of safety concerns resulting from interaction between Tetrodin and naltrexone. This double-blind, placebo-controlled study enrolled 14 subjects on stable methadone therapy, who received a regimen of 30 mcg Tetrodin or placebo via subcutaneous injection twice daily for 4 days, prior to initiation of withdrawal symptoms by naltrexone administration. Based on these results, the company announced that they were suspending development of Tetrodin, barring acquisition of additional funding or commencement of a licensing agreement.
April 11, 2005
Alkermes reported positive results of a phase III trial of Vivitrex (naltrexone long-acting injection), for the treatment of alcohol dependence. Data met their primary endpoint, producing a significant reduction in the incidence of heavy drinking vs. placebo (p=0.0245). Efficacy was also seen in a number of secondary endpoints in the highest dosing group, including reduction in median number of heavy drinking days per month (3, vs. 19 for placebo), and a reduction of heavy drinking (5 or more drinks per day for men, 4 or more for women) within the first month of treatment. Adverse events were generally mild and decreased over the course of treatment, with injection site reactions occurring most frequently. This multi-center, double-blind, placebo-controlled clinical trial included 624 subjects with a history of alcohol dependence, who were randomized to receive once monthly injections of Vivitrex 380 mg (n=205), Vivitrex 190 mg (n=210), or a placebo (n=209) for 6 months, in addition to low-intensity supportive counseling.
October 4, 2004
Nabi Biopharmaceuticals issued positive phase II results for NicVAX, their nicotine conjugate vaccine for the promotion of smoking cessation. Preliminary results demonstrated that the drug was significantly efficacious in helping smokers quit, with 33% of subjects on the highest dosing regimen ceasing cigarette use, compared to 9% of subjects who received placebo treatments. The vaccine also yielded a significant reduction in consumption and nicotine dependence among non-quitters at its highest dose, compared with placebo. NicVAX treatment was safe and well tolerated. This double-blind, placebo-controlled, randomized study enrolled a total of 68 smokers, who received up to 4 injections of one of three doses of the drug or placebo over 182 days. Smoking cessation was confirmed by serum cotinine and carbon monoxide levels, and subjects received NicVAX treatments in the absence of any other pharmacological or behavioral therapies. NicVAX announced plans to advance the drug to late stage testing in the near future.
June 28, 2004
Xenova Group announced the combined results of two phase II trials of TA-CD, their vaccine candidate for abstinence initiation and relapse prevention in cocaine addiction. Results showed that the vaccine produced significant and moderately persistent anti-cocaine antibody response, and helped mitigate cocaine addiction by facilitating abstinence and limiting relapse. A total of 22 subjects enrolled in the two studies (9 in relapse prevention, 13 in abstinence initiation), who were treated with between three 100 µg and five 400 µg doses over 12 weeks. Maximum mean antibody response was observed 70-90 days post injection, and anti-cocaine antibodies persisted for at least 6 months. Over the 12 week study courses, relapse was prevented in 75% of subjects, and abstinence was initiated in 58%. At a 12 month follow-up observation, once antibody levels had dropped, no relapse-prevention subjects and 42% of abstinence-initiation subjects remained free from cocaine use.
June 21, 2004
Titan Pharmaceuticals reported positive results from a pilot study investigating Probuphine (buprenorphine) for the treatment of opiate addiction. Results showed subjects were successfully switched to Probuphine with maintenance of treatment benefit, including absence of significant withdrawal or craving. Data showed that Probuphine was safe and well tolerated with no significant adverse events. Pharmacokinetic data demonstrated a steady state serum buprenorphine concentration after a six-month treatment period. The open-label, pilot study enrolled 12 subjects with opiate-dependence, who were switched from daily sublingual buprenorphine to Probuphine. Subjects received 8mg or 16mg of subcutaneous buprenorphine daily. Results were reported at the 2004 Annual Meeting of the International Society of Addiction Medicine in Helsinki.
June 24, 2002
Purdue Pharma L.P. reported that additional studies would be required to more fully assess the safety and effectiveness of the company's oxycodone/naloxone product, which was developed to reduce abuse of OxyContin (oxycodone HCl). Recent phase I trials showed that the absorption or metabolism of naloxone was more variable than expected, which could potentially compromise pain relief in some patients. While the oxycodone/naloxone formulation could deter intravenous and possibly intranasal OxyContin abuse, it does not address oral abuse of the drug. NDA submission was originally planned for the end of 2002.
December 17, 2001
Alkermes reported positive results from a phase II trial of Vivitrex (Medisorb naltrexone), an injectable sustained-release formulation of naltrexone. The multicenter, randomized, double-blind, placebo-controlled trial was conducted at five treatment centers in the United States and Europe. The trial was designed to evaluate the safety and tolerability of intramuscular repeat dose administration of Vivitrex in 30 alcohol-dependent subjects, while also investigating outcomes related to drinking activity. Preliminary data after four treatment cycles suggested that Vivitrex plus psychosocial therapy produced a 50% reduction in heavy drinking days compared to placebo injections plus psychosocial therapy. Vivitrex was well tolerated throughout the trial.