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Drug Interaction Study With BI 201335 and Methadone or Buprenorphine/Naloxone

Primary Purpose

Hepatitis C

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

BI 201335

About this trial

This is an interventional treatment trial for Hepatitis C

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

stable dose of either methadone or buprenorphine/naloxone for 30 days for opioid maintenance therapy.
Male and female volunteers with a body mass index (BMI) = 18.5 and < 32 with a minimum weight of 50kg.

Exclusion criteria:

any other significant medical illness of clinical significance.
history of rash or photosensitivity
chronic or acute infections including HIV, hepatitis B and hepatitis C.
history of allergy considered significant for this study
intake of any other medications except for methadone or buprenorphine/naloxone.
QTc on electrocardiogram (ECG) > 470.
use of any other investigational drug within 30 days of the study.
drug or alcohol abuse (other than the defined opioid maintenance therapy with either methadone or buprenorphine/naloxone)
blood donation of more than 100mL within four weeks of the trial.
excessive physical activities one week prior to and during the trial.
any clinically relevant laboratory value.
concomitant use of any food product known to alter P450 or P-gp activity such as grapefruit juice, seville oranges and St. John's Wort.
inadequate venous access
For women of childbearing potential:
pregnancy or planning to become pregnant within 3 months of the trial
positive pregnancy test at screening visit
no proof of sterilization or unwilling or unable to use a double barrier method of birth control during the study and up to 3 months after the study.
lactation with active breastfeeding from screening up to 30 days after last study visit.

Sites / Locations

1220.57.0001 Boehringer Ingelheim Investigational Site
1220.57.0002 Boehringer Ingelheim Investigational Site
1220.57.0003 Boehringer Ingelheim Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Methadone group

Buprenorphine

Arm Description

patients on stable methadone therapy (at least 30 days) up to a maximum of 180mg per day

patients on stable buprenorphine/naloxone therapy (at least 30 days) up to a maximum dose of 24mg/6mg per day.

Outcomes

Primary Outcome Measures

R-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.

These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours.

R-methadone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9.

These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state.

R-methadone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9.

These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose

S-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9

These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours.

S-methadone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9

These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state.

S-methadone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9

These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose

Buprenorphine: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.

These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours.

Buprenorphine: Geometric Mean Steady-state Cmax on Day 1 and on Day 9.

These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state.

Buprenorphine: Geometric Mean Steady-state C24hr on Day 1 and on Day 9.

These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose

Norbuprenorphine: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.

These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours.

Norbuprenorphine: Geometric Mean Steady-state Cmax on Day 1 and on Day 9.

These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state.

Norbuprenorphine: Geometric Mean Steady-state C24hr on Day 1 and on Day 9.

These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose

Naloxone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.

These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours.

Naloxone: Geometric Mean Steady-state Cmax on Day 1 and on Day 9.

These are the unadjusted summary statistics on the original scale for the maximum measured concentration of faldaprevir in plasma at steady state.

Naloxone: Geometric Mean Steady-state C24hr on Day 1 and on Day 9.

These are the unadjusted summary statistics on the original scale for steady-state plasma concentration of faldaprevir 24 hours after the last dose

Secondary Outcome Measures

Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Objective Opiate Withdrawal Scale (OOWS)-Change From Baseline

The OOWS is conducted by a trained independent examiner for either the presence or absence of the following symptoms during a 10 minute observation period at designated times during the trial. The minimum possible OOWS score is 0 and the maximum possible score is 13. Objective criteria: Yawning, Rhinorrhoea, Piloerection, perspiration, lacrimation, mydriasis, hot and cold flushes, restlessness, vomiting, tremors, anxiety, muscle twitches, abdominal cramps. Higher score indicates increasing severity of opiate withdrawal syndrome.

Pharmacodynamic Assessment of Withdrawal From Either Methadone or Buprenorphine/Naloxone Using the Subjective Opiate Withdrawal Scale (SOWS)-Change From Baseline

The SOWS is a subjective scale self-evaluated by the subject. The SOWS shows items reflecting the common motor, autonomic, gastrointestinal, musculo-skeletal, and psychic symptoms of opiate withdrawal. Subjects are instructed to rate each symptom on a scale of 0 to 4 (0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely) at designated times [c.f. Section 3.1]. The minimum possible SOWS score is 0, the maximum 64. The following subjective criteria are answered by the subject using the scale below: 1) I feel anxious, 2) I feel like yawning 3) I am perspiring, 4) My eyes are watering, 5) My nose is running, 6) I have goose flesh, 7) I am shaking 8) I have hot flushes, 9) I have cold flushes, 10) My bones and muscles ache, 11) I feel restless, 12) I feel nauseous, 13) I feel like vomiting, 14) My muscles twitch, 15) I have cramps in my stomach, 16) I feel like shooting up now. Higher score indicates increasing severity of opiate withdrawal syndrome.

Full Information

NCT ID

NCT01637922

First Posted

July 9, 2012

Last Updated

July 3, 2015

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT01637922

Brief Title

Drug Interaction Study With BI 201335 and Methadone or Buprenorphine/Naloxone

Official Title

Effect of Multiple Dosing With BI 201335 on the Safety, Pharmacokinetics and Pharmacodynamics of Steady-state Methadone and Buprenorphine/Naloxone in Subjects on Stable Addiction Management Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

July 2015

Overall Recruitment Status

Completed

Study Start Date

August 2012 (undefined)

Primary Completion Date

November 2012 (Actual)

Study Completion Date

November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

Brief Summary

Otherwise healthy subjects who are currently bein maintained on either methadone or buprenorphine/naloxone for opioid maintenance therapy who have been on a stable dose for at least 30 days will be administered BI 201335 daily to determine if a drug interaction occurs between BI 201335 and either methadone or buprenorphine/naloxone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Methadone group

Arm Type

Active Comparator

Arm Description

patients on stable methadone therapy (at least 30 days) up to a maximum of 180mg per day

Arm Title

Buprenorphine

Arm Type

Active Comparator

Arm Description

patients on stable buprenorphine/naloxone therapy (at least 30 days) up to a maximum dose of 24mg/6mg per day.

Intervention Type

Drug

Intervention Name(s)

BI 201335

Intervention Description

BI 201335 for 9 days

Intervention Type

Drug

Intervention Name(s)

BI 201335

Intervention Description

BI 201335 for 9 days

Primary Outcome Measure Information:

Title

R-methadone: Geometric Mean Steady-state AUC0-24 on Day 1 and on Day 9.

Description

These are the unadjusted summary statistics on the original scale for area under the concentration time curve (AUC) of faldaprevir in plasma over a uniform dosing interval from 0 to 24 hours.

Time Frame