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Evaluation of QTc IntervalPhase 4NCT04088266

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.

A Phase 4 study testing 16 mg buprenorphine with 4 mg naloxone sublingual film in people with Evaluation of QTc Interval, run by Teva Pharmaceuticals USA.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Evaluation of QTc Interval
What is being tested?
16 mg buprenorphine with 4 mg naloxone sublingual film
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jan 2020to Dec 2020
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • 9. Use of anticholinergic drugs within 7 days before Induction.
  • Use of diuretics within 7 days before Induction.
  • Suicidal ideation within 30 days prior to Screening as assessed by answering "yes" to questions 4 or 5 on the suicidal ideation portion of the C-SSRS. A suicide attempt, interrupted attempt, aborted attempt, or preparatory acts/behavior within 6 months before Screening will also result in exclusion.
  • 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.
  • History of congenital or acquired Long QT syndrome (LQTS), Torsade de Pointes (TdP), or an immediate family member with this condition.
  • Use of Class IA antiarrhythmic medications (e.g., quinidine, procainamide, disopyramide), Class IC antiarrhythmic medications (e.g., flecainide, propafenone), Class III antiarrhythmic medications (e.g., sotalol, amiodarone, dofetilide, ibutilide, dronedarone) or other medications that prolong the QT interval within 28 days before Induction.
  • Significant history of chronic hypokalemia, hypomagnesaemia, hypocalcaemia or any electrolyte abnormality that can prolong the QTc interval.
  • Any clinically significant finding on physical exam, clinical labs or ECG that, in the opinion of the Investigator, would compromise the safety of the subject or the integrity of the study.
  • History of hypotensive episodes or evidence at screening of orthostatic hypotension. This is defined as either a drop in systolic blood pressure of at least 20 mm Hg or a drop in diastolic blood pressure of at least 10 mm Hg, following a resting supine period of 5 min and a subsequent 2-5 min period of quiet standing.
  • History of syncopal episodes.
  • Use of pharmacologic agents known to induce or inhibit Cytochrome P450 3A4 within 30 days before Induction to an extent that, in the opinion of the Investigator, would compromise the safety of the subject or the integrity of the study.
  • Use of monoamine oxidase inhibitors (MAOI) within 14 days before Induction.
  • Use of serotonergic drugs within 30 days before Induction. These include, but aren't limited to, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), 5-HT3 receptor antagonists, and other medications that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazadone, tramadol). Triptans (e.g., sumatriptan, zolmitriptan, etc) are permitted at the discretion of the Investigator.
  • Use of buprenorphine products within 14 days before Induction.
  • Use of the following CNS depressants within 14 days before Induction: methadone, alcohol, benzodiazepines, barbiturates, tranquilizers, and non-benzodiazepine sedatives (e.g., eszopiclone, zaleplon, zolpidem, doxepin, ramelteon, suvorexant). Muscle relaxants will be permitted at the discretion of the Investigator.
  • Donation or significant loss of whole blood (480 mL or more) within 30 days or plasma within 14 days before inpatient admission.
  • Positive test results for HIV, active Hepatitis B (+ HBsAg and +anti-HBc IgM) or active Hepatitis C (asymptomatic Hepatitis C is not excluded).
  • An ALT or AST level that is greater than three times the upper limit of normal value.
  • Safety laboratory values, including liver function, that in the opinion of the Investigator would compromise subject safety or pose excessive risk of hepatic events.
  • Any surgery within 6 months before Screening that, in the opinion of the Investigator, would compromise the safety of the subject or the integrity of the study.
  • Receipt of any drug as part of a research study within 30 days before Screening.
  • Positive testing for methadone at Screening.
  • Positive testing for alcohol, buprenorphine, methadone, hydrocodone, cocaine, amphetamines (including methamphetamine and MDMA), benzodiazepines, or barbiturates prior to beginning Induction on Day -7.
  • Positive testing for alcohol, methadone, hydrocodone,cocaine, amphetamines (including methamphetamine and MDMA), benzodiazepines, or barbiturates prior to beginning Confinement on Day -2. The only exception will be for benzodiazepines given under the direction of the Investigator in order to treat symptoms of withdrawal.
  • Employees of the Investigator or research center or their immediate family members.
  • Inability to understand the requirements of the study and the relative information and are unable or not willing to comply with the study protocol.

About this study

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.

Being tested
16 mg buprenorphine with 4 mg naloxone sublingual film

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 16 mg buprenorphine with 4 mg naloxone sublingual filmCombination product

    CASSIPA®

Study groups in NCT04088266
Study groupRoleWhat they receive
16 mg buprenorphine with 4 mg naloxone sublingual filmOtherCASSIPA® sublingual film 16 mg buprenorphine with 4 mg naloxone
Receives: Combination Product: 16 mg buprenorphine with 4 mg naloxone sublingual film

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 10 days

Secondary outcomes (1)

  1. Potential for delayed effects

    Differences in QTcF between baseline and post-dose treatment

    Measured: 60 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Sep 2019
  2. Study startJan 2020 (estimated)
  3. Primary completionDec 2020 (estimated)
  4. Study completionDec 2020 (estimated)

Why it stopped: Study delayed indefinetly

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04088266
Sponsor's protocol ID
71936002
Status last verified
Oct 2020
First submitted
10 Sep 2019
Last updated
8 Oct 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing 16 mg buprenorphine with 4 mg naloxone sublingual film in people with Evaluation of QTc Interval, run by Teva Pharmaceuticals USA.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Differences in QTcF between baseline and post-dose treatment (time frame: 10 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04088266.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.

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