An Open-Label, Single-Center Study to Evaluate the Exposure-Response Relationship Between the Plasma Drug Concentrations and the Change From Baseline in QTc at Steady State Following Once-daily Administration of CASSIPA® in Opioid Dependent Subjects.

NCT04088266 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: 71936002
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of this study is to evaluate the exposure-response relationship between the steady-state plasma concentrations of buprenorphine, norbuprenorphine, naloxone, and total naloxone and the change from baseline in QTc prolongation intervals following administration of CASSIPA® sublingual film (16 mg buprenorphine with 4 mg naloxone) to male and female adult subjects initiating treatment of opioid dependence.

Conditions

Evaluation of QTc Interval

Outcome Measures

Primary Outcomes (1)

• Differences in QTcF between baseline and post-dose treatment

  Differences between QTcF at each post-treatment time point on Day 1 and Day 10 relative to the baseline on Day -7 (ΔQTcF) will be calculated for every subject.

  10 days

Secondary Outcomes (1)

• Potential for delayed effects

  60 days

Study Arms (1)

16 mg buprenorphine with 4 mg naloxone sublingual film

OTHER

CASSIPA® sublingual film 16 mg buprenorphine with 4 mg naloxone

Combination Product: 16 mg buprenorphine with 4 mg naloxone sublingual film

Interventions

16 mg buprenorphine with 4 mg naloxone sublingual film COMBINATION_PRODUCT

CASSIPA®

16 mg buprenorphine with 4 mg naloxone sublingual film

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or non-pregnant, non-lactating female, 18-60 years of age (inclusive), with a Body Mass Index (BMI) of 18.0-35.0 kg/m2 (inclusive).
• Seeking initiation of treatment for opioid dependence.
• Signed informed consent form, which meets all criteria of current Food and Drug Administration (FDA) regulations.
• Female subjects who are of non-childbearing potential must meet one of the following criteria:
• surgically sterile (e.g., bilateral oophorectomy, tubal ligation, hysterectomy or permanent sterilization procedures), with the procedure performed at least 3 months before the start of Induction
• naturally postmenopausal (no menses) for at least 1 year before Induction and/or has a documented FSH level ≥ 40 mIU/mL at Screening
• Female subjects of childbearing potential must not be pregnant or lactating at Screening as confirmed by a negative quantitative serum pregnancy test with a sensitivity of 5 mIU/mL of human chorionic gonadotropin. Females of childbearing potential must have negative urine pregnancy tests with a sensitivity of 25 mIU/mL at the start of Induction (Day -7), the start of Confinement (Day -2), and at all Follow Up outpatient visits. Women of childbearing potential must agree to the use of a reliable method of contraception (e.g., total abstinence, intrauterine device, a double-barrier method, oral, transdermal, injected or implanted non- or hormonal contraceptive), throughout the study. A sterile sexual partner is not considered an adequate form of birthcontrol. Subjects on hormonal contraceptives must have been on the same hormonal contraceptive for at least one month before Screening and continue throughout the duration of the study.
• Has a diagnosis of moderate to severe opioid use disorder per the DSM-5 criteria.
• Has a Clinical Opiate Withdrawal Scale (COWS) score of greater than 12 at the start of the Induction period and a COWS score of less than 5 at the start of the Dosing period.
• Has successfully completed the Induction period of the study to continue on to the Dosing period.

You may not qualify if:

• Females who are pregnant, lactating or likely to become pregnant during the study.
• Has a diagnosis of moderate to severe substance use disorder, by DSM-5 criteria, for any substances other than opioids or tobacco.
• Requires opioid treatment for any ongoing medical condition.
• Has sustained a traumatic brain injury (TBI) within 30 days prior to Screening, which, in the opinion of the Investigator, would compromise the safety of the subject or the integrity of the study.
• Significant history or current medical condition associated with increased intracranial or cerebrospinal fluid pressure such as intracranial neoplasm, hydrocephalus, idiopathic intracranial hypertension, or a related condition which, in the opinion of the Investigator, would compromise the safety of the subject or the integrity of the study.
• Significant history or current medical condition associated with increased intracholedochal pressure such as choledocholithiasis or a related condition which, in the opinion of the Investigator, would compromise the safety of the subject or the integrity of the study.
• Significant history or current medical condition compromising respiratory function such as COPD, moderate to severe persistent asthma, cor pulmonale, or a related condition which, in the opinion of the Investigator, would compromise the safety of the subject or the integrity of the study.
• Use of antiretroviral drugs within 28 days before Induction.
• \. Use of anticholinergic drugs within 7 days before Induction.
• Use of diuretics within 7 days before Induction.
• History of allergy or hypersensitivity to buprenorphine, naloxone, any component of the drug delivery system, other opioids, or history of any drug hypersensitivity or intolerance which, in the opinion of the Investigator, would compromise the safety of the subject or the integrity of the study.
• Significant history or current medical condition or organ dysfunction that in the opinion of the Investigator would compromise the safety of the subject or the integrity of the study, including but not limited to cardiovascular, neurologic, pulmonary, gastrointestinal, hepatic, renal, endocrine, psychiatric and infectious disease.
• Diagnosed or treated for cancer within the last 5 years.
• History or evidence at Screening of clinically significant 12-lead ECG abnormalities or cardiac arrhythmias (including, but not limited to, significant 1st degree atrioventricular (AV) block, 2nd or 3rd degree AV block, complete left bundle branch block (LBBB), QRS duration \> 120 ms, prior evidence of MI) that, in the opinion of the Investigator, would compromise the safety of the subject or the integrity of the study; or a QTc \> 450 ms for males and \> 470 ms for females using Fredericia formula. ECGs may be repeated as appropriate to confirm values and rule out extraneous results, at the discretion of the Investigator.
• History of clinically unstable cardiac disease, including uncontrolled hypertension, unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, myocardial infarction, active myocardial ischemia, or left ventricular hypertrophy.

Sponsors & Collaborators

• Teva Pharmaceuticals USA: lead

MeSH Terms

Interventions

Buprenorphine

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2019
• First Posted: September 12, 2019
• Study Start: January 1, 2020
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: October 8, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share