Evaluation of the Tolerability of Switching Subjects on Chronic ATC Opioid Therapy to Buprenorphine HCl Buccal Film

NCT01871285 | Completed Phase 2 Results

• 1 other identifier: EN3409-204
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 3

Brief Summary

The primary aim of this study is to determine if chronic pain subjects on around-the-clock opioids who are receiving 100 to 220 mg oral morphine sulfate equivalent (MSE) can be safely transitioned on to buprenorphine hydrochloride (HCl) buccal film at 50% of their MSE dose without inducing opioid withdrawal or reversing analgesic effects.

Conditions

Pain

Keywords

ATC, Opioid, withdrawal, switch

Outcome Measures

Primary Outcomes (3)

• Number of Responders

  A responder is defined as a subject whose maximum (across all time points) clinical opiate withdrawal scale (COWS) total score is ≥13. COWS scores range 0 to 4 or 5 on 11 items related to opiate withdrawal signs or symptoms; total score range 0 to 48 where 0-4 = no withdrawal and 5-12 = mild, 13-24 = moderate, 25-36 = moderately severe, more than 36 = severe withdrawal.

  Pre-dose (-0.5), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 12.5, 13, 13.5, 14, 16, and 24 (or end of study visit) hours post 1st study drug dose on each day of administration (period 1 [day 1] and period 2 [day 2]) in each treatment sequence

• Maximum COWS Total Score

  Investigator-rated COWS scores range 0 to 4 or 5 on 11 items related to opiate withdrawal signs or symptoms; total score range 0 to 48 where 0-4 = no withdrawal and 5-12 = mild, 13-24 = moderate, 25-36 = moderately severe, more than 36 = severe withdrawal. The maximum COWs total score is defined as the maximum COWs total score across all time points during the corresponding treatment period after study drug administration for each subject.

  Pre-dose (-0.5), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 12.5, 13, 13.5, 14, 16, and 24 (or end of study visit) hours post 1st study drug dose on each day of administration (period 1 [day 1] and period 2 [day 2]) in each treatment sequence

• Change From Baseline in Maximum COWS Total Score

  Investigator-rated COWS scores range 0 to 4 or 5 on 11 items related to opiate withdrawal signs or symptoms; total score range 0 to 48 where 0-4 = no withdrawal and 5-12 = mild, 13-24 = moderate, 25-36 = moderately severe, more than 36 = severe withdrawal. The change from baseline in maximum COWS total score is determined as the difference between the maximum COWs total score and the baseline COWs total score.

  Pre-dose (-0.5; baseline), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 12.5, 13, 13.5, 14, 16, and 24 (or end of study visit) hours post 1st study drug dose on each day of administration (period 1 [day 1] and period 2 [day 2]) in each treatment sequence

Secondary Outcomes (2)

• Change From Baseline in COWS Total Score Over Time

  Pre-dose (-0.5; baseline), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 12.5, 13, 13.5, 14, 16, and 24 (or end of study visit) hours post 1st study drug dose on each day of administration (period 1 [day 1] and period 2 [day 2]) in each treatment sequence

• Change From Baseline in "Pain Now" Over Time Using NRS

  Pre-dose (-0.5; baseline), 0.5, 1, 2, 4, 9, 12, 12.5, 13, 14, 16, and 24 (or end of study visit) hours post 1st study drug dose on each day of administration (period 1 [day 1] and period 2 [day 2]) in each treatment sequence

Study Arms (2)

MSE Dose Group 1

EXPERIMENTAL

Morning and evening dose of buprenorphine HCl buccal film (300 μg) + placebo capsule in one period, and then placebo film + over-encapsulated ATC opioid (morphine sulfate or oxycodone) at 50% MSE daily dose in the alternate period

Drug: Buprenorphine; Drug: Placebo film; Drug: Oxycodone; Drug: Morphine sulfate; Drug: Placebo capsule

MSE Dose Group 2

EXPERIMENTAL

Morning and evening dose of buprenorphine HCl buccal film (450 μg) + placebo capsule in one period, and then placebo film + over-encapsulated ATC opioid (morphine sulfate or oxycodone) at 50% MSE daily dose in the alternate period

Drug: Buprenorphine; Drug: Placebo film; Drug: Oxycodone; Drug: Morphine sulfate; Drug: Placebo capsule

Interventions

Buprenorphine DRUG

Also known as: Buprenorphine buccal film, Buprenorphine HCl buccal film, EN3409, BEMA Buprenorphine, BELBUCA

MSE Dose Group 1; MSE Dose Group 2

Placebo film DRUG

Matching placebo buccal film

Also known as: Placebo buccal film, BEMA placebo

MSE Dose Group 1; MSE Dose Group 2

Oxycodone DRUG

Oxycodone extended-release (ER) or immediate-release (IR) 5, 10, 15, 20, and 30 mg over-encapsulated oral tablets

Also known as: Oxycodone tablets, OxyContin, Oxycodone IR

MSE Dose Group 1; MSE Dose Group 2

Morphine sulfate DRUG

Morphine sulfate 15, 30, and 60 mg ER or 15 and 30 mg IR over-encapsulated oral tablets

Also known as: Morphine sulfate tablets, MS Contin, Morphine sulfate IR

MSE Dose Group 1; MSE Dose Group 2

Placebo capsule DRUG

Oral placebo capsules matching the over-encapsulated morphine sulfate and oxycodone tablets

Also known as: Matching placebo capsules

MSE Dose Group 1; MSE Dose Group 2

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained prior to any study-related procedure being performed
• Male or non-lactating female subjects 18 to 60 years of age at time of consent
• Female subjects who are non-pregnant on the basis of screening serum pregnancy test and who are practicing abstinence or using a medically acceptable form of contraception (eg, intrauterine device, hormonal birth control, or double barrier method) or have been post-menopausal, biologically sterile, or surgically sterile (ie, hysterectomy, bilateral oophorectomy, or tubal ligation) for more than 1 year
• Male subjects who are practicing abstinence, surgically sterile or are using a medically acceptable form of contraception
• Subjects with a ≥6 months history of chronic pain (including peripheral neuropathic pain) requiring ATC opioid therapy with ≥80 mg but ≤220 mg MSE per day for at least 28 days
• Receiving one of the following opioids ATC for ≥28 days: (i) Morphine Sulfate; (ii) Oxycodone hydrochloride
• Displays signs and symptoms of withdrawal (ie, COWS score ≥5) within 5 minutes following naloxone challenge
• Able to understand the study procedures, complete the assessment scales, and communicate meaningfully with study personnel
• Stable health, as determined by the Principal Investigator, on the basis of medical history, physical examination, and screening laboratory results

You may not qualify if:

• Inability to meet study participation requirements, including two 2-night stays with pharmacokinetic sampling
• A history or current evidence of clinically significant pulmonary (eg, asthma, chronic obstructive pulmonary disease, cor pulmonale or severe bronchial asthma ), gastrointestinal, hepatic, renal, hematologic, immunologic, endocrine, neurologic, oncologic or psychiatric disorder or any other condition, including evidence of abnormalities on physical examination, abnormal vital signs, electrocardiogram (ECG), or clinical laboratory values which in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results
• Supine systolic blood pressure \>180 mm Hg or \<90 mm Hg or diastolic blood pressure \> 105 mm Hg or \<50 mm Hg at screening (may be repeated once)
• COWS score greater than 4 prior to the screening naloxone challenge
• Aspartate aminotransferase or alanine aminotransferase \>3 times the upper limits of normal or serum creatinine \>1.9 mg/dL at Screening, or any laboratory abnormality which, in the opinion of the Investigator, would contraindicate study participation
• Use of monoamine oxidase inhibitors within 14 days of screening or during the study
• Use of any medication, nutraceutical or herbal product with cytochrome P450 3A4 inhibition or induction properties within the past 30 days
• Donation of 450 mL or more of blood within 30 days prior to screening or a hemoglobin value \<11.0 g/dL at screening
• Documented history of alcohol and/or substance abuse (excluding nicotine and/or caffeine) within 5 years prior to screening, and/or is currently in treatment or is seeking treatment for alcohol and/or substance abuse, as assessed by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria
• Positive alcohol breath test at screening
• Positive urine toxicology screen for drugs of abuse at screening
• History of hypersensitivity, allergy, or contraindication to any opioid or clinically significant intolerance to buprenorphine or naloxone
• History of seizures, convulsions, or increased intra-cranial pressure (history of pediatric febrile seizures is permitted)
• History of significant head injury within 6 months of screening
• Any clinically significant abnormality of the buccal mucosa which could impact drug absorption

Sponsors & Collaborators

• BioDelivery Sciences International: lead

Study Sites (3)

Vince and Associates Clinical Research, Inc.

Overland Park, Kansas, 66212, United States

Location

CRI Lifetree

Philadelphia, Pennsylvania, 19139, United States

Location

CRI Lifetree (Lifetree Clinical Research)

Salt Lake City, Utah, 84106, United States

Location

MeSH Terms

Conditions

Pain; Ataxia Telangiectasia

Interventions

Buprenorphine; Oxycodone; Morphine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Spinocerebellar Ataxias; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Ataxia; Dyskinesias; Telangiectasis; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Primary Immunodeficiency Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

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; Codeine; Morphine Derivatives

Results Point of Contact

• Title: Clinical Trial Coordinator
• Organization: Endo Pharmaceuticals Inc.

clinicalsite.inquiries@endo.com

Study Officials

• Todd Kirby, PhD

  Endo Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2013
• First Posted: June 6, 2013
• Study Start: June 1, 2013
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: February 27, 2017
• Results First Posted: February 3, 2016

Record last verified: 2017-01

Locations

US (3)