A Companion Treatment Study for Patients With Moderate to Severe Acne Vulgaris

Inclusion Criteria: Male or female patients will be considered eligible for participation in the study if allof the following inclusion criteria are satisfied prior to randomization:

1. Has completed and signed an appropriately administered Informed Consent Form (ICF)prior to any study-related procedures. Patients less than 18 years of age (or asrequired by state law) must sign an Assent Form for the study and a parent or legalguardian must sign the ICF.
2. Is 12 years of age or older.
3. Has facial acne vulgaris with an IGA score of moderate (3) or severe (4).
4. Is willing and able (with assistance from a caregiver as necessary) to both applyAMZEEQ® and take oral isotretinoin capsule(s) as directed, comply with studyinstructions, and commit to all follow-up visits for the duration of the study.
5. If female of child-bearing potential (FOCBP), must have two negative pregnancy tests,one being serologic, within the screening period.
6. Is willing to commit to true abstinence from heterosexual contact (which must bereviewed at each study visit and source documented) or agreed to use, and be able tocomply with, effective contraception without interruption, prior to starting treatmentas detailed below, during study period. For FOCBP who may participate in the study,the following methods of contraception, if properly used, are generally consideredreliable with the following wait periods prior to having relations: oralcontraceptives; vaginal contraceptive ring and patch contraceptives (one full cycle;e.g., 4 to 8 weeks); injection contraceptives (more than 7 days); intrauterine deviceor implantable hormone contraceptives (more than 7 days); surgical sterilization (bilateral tubal ligation) or a vasectomized partner (each, more than 6 months); malecondom with intravaginal spermicide or diaphragm/cervical cap with spermicide (effective with proper use without a waiting period).
7. If sexually active male patient, must practice true abstinence (which must be reviewedat each study visit) or agree to use a condom with intravaginal spermicide duringsexual contact with a pregnant female or a FOCBP, while participating in the study,during dose interruptions, and for at least 30 days following treatmentdiscontinuation, unless patient has undergone a successful vasectomy. Male patientsshould refrain from making sperm donations at any time during study participation andfor at least 30 days following treatment discontinuation.
8. Is willing to minimize exposure of the treated skin to ultraviolet light (e.g. avoidexcessive sunlight, agree to not use tanning beds) and extremes in weather, such aswind or cold, throughout the study.
9. In the investigator's opinion, patient is in good general health and is free of anydisease state or physical condition that exposes the patient to an unacceptable riskby study participation or impairs the evaluation of the patient or the treatments byparticipating in the study.

Exclusion Criteria: Patients who meet any of the following will be excluded from the study:

1. Female who is pregnant, lactating or breastfeeding, or is planning a pregnancy duringthe study.
2. Acne conglobata, acne fulminans, secondary acne (chloracne, drug-induced acne), or anydermatological condition of the face (such as seborrhea, atopic dermatitis or basalcell carcinoma) that would require the use of confounding therapies or facial hair (eg, beard, sideburns, mustache) that could either interfere with clinicalevaluations.
3. Sunburn on the face.
4. Severe systemic disease that might interfere with the conduct of the study or theinterpretation of the results.
5. Abnormal Screening laboratory values that are considered clinically significant.
6. Patient is currently enrolled in another investigational drug or device study or isusing or has used an investigational drug or investigational device treatment within 30 days of randomization.
7. Patient, who in the opinion of the investigator, is unable or unlikely to comply withthe requirements of the study protocol.
8. Patients who have a history of any of the following will be excluded:

• Allergy to tetracycline-class antibiotics or to any ingredient in the study drug
• Pseudomembranous colitis or antibiotic-associated colitis
• Hepatitis or liver damage or renal impairment
• Known or suspected premalignant or malignant disease (excluding successfullytreated skin cancers)

9. Patients who have used the following medications (topical refers only to the facialarea) will not be eligible:

• Within 1 week prior to randomization:
• Medicated facial cleansers
• Topical acne treatments (other than those listed below)
• Within 4 weeks prior to randomization:
• Topical retinoids on the face
• Topical anti-inflammatories eg, PDE-4 inhibitors, calcineurin inhibitors andcorticosteroids on the face
• Topical corticosteroids on body areas other than the face for more than 15consecutive days and on more than 10% of body surface area. In flexural bodyareas, such as axillary and inguinal regions, only mild topicalcorticosteroids and allowed for short term use (≤15 consecutive days).
• Systemic antibiotics
• Systemic acne treatments
• Within 12 weeks prior to randomization:
• Systemic retinoids
• Systemic corticosteroids (Note: Intranasal and inhaled corticosteroids maybe used throughout the study).

10. The following medications have been used less than the specified length of stableusage and patients must not initiate or change the dosing regimen during the course ofthe study: 3 months: hormonal contraceptives and therapies which also includetestosterone replacement or supplementation.
11. Patient has any acute illness (eg, infection) within 48 hours of randomization, which,in the investigator's opinion, is considered significant.
12. Patient has a history of sensitivity to any of the ingredients in the medications.
13. Documented history of depression or self-harm that is not, in the opinion of theInvestigator, currently adequately controlled with medication or in remission. Or, thepresence of significant uncontrolled neuropsychiatric disorder, are clinically judgedby the investigator to be at risk for suicide, or have a "yes" answer to any of thefollowing at Screening or Baseline:
14. Question 4 (Active Suicidal Ideation with Some Intent to Act, Without SpecificPlan) on the "Suicidal Ideation" portion of the Columbia Suicide Severity RatingScale (C-SSRS) or
15. Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the C-SSRS or
16. Any of the suicide-related behaviors (actual attempt, interrupted attempt,aborted attempt, preparatory act or behavior) on the "Suicidal Behavior"portionof the C-SSRS. Note: A patient does not necessarily have to be excluded if they have self-injuriousbehavior that would be classified as non-suicidal self-injurious behavior. If thissituation arises, the subject should be referred to a psychiatrist or appropriatelytrained professional as indicated.
17. Drug addiction or alcohol abuse (within the last 2 years).
18. Patient has history of previous use of isotretinoin.