A Trial to Evaluate the Abuse Potential of 3 Doses of GRT6005 in Adult Non-dependent Recreational Opioid Users

NCT03757559 | Completed Phase 1 DMC

• 1 other identifier: HP6005/10
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study was to evaluate the abuse potential of single doses of cebranopadol (GRT6005) relative to hydromorphone (immediate-release formulation \[IR\] and placebo in 48 non-dependent recreational opioid users. Secondary objectives were to evaluate the abuse potential of hydromorphone IR compared to placebo (trial validation), to evaluate the safety and tolerability of single doses of cebranopadol (200, 400, and 800 micrograms), and to evaluate pharmacokinetics (PK) of cebranopadol and optionally some of its metabolites.

Conditions

Abuse, Drug

Keywords

Cebranopadol; Hydromorphone; Drug liking

Outcome Measures

Primary Outcomes (1)

• Drug Liking (at this moment)

  Visual analog scale (VAS) rating; Question text: At this moment, my liking for this drug is ...; Bipolar response anchors: 0 (Strong disliking), 50 (Neither like nor dislike), 100 (strong liking).

  At 16 distinct time points between 30 minutes and 56 hours after drug intake

Secondary Outcomes (16)

• Any Drug Effects

  At 16 distinct time points between 30 minutes and 56 hours after drug intake

• Good Drug Effects

  At 16 distinct time points between 30 minutes and 56 hours after drug intake

• Bad Drug Effects

  At 16 distinct time points between 30 minutes and 56 hours after drug intake

• High

  Pre-dose and at 16 distinct time points between 30 minutes and 56 hours after drug intake

• Take Drug Again

  At 12, 24, and 56 hours aft drug intake

Other Outcomes (3)

• Area under the concentration-time curve up to the sampling time t (AUC0-t)

  From pre-dose until 56 hours post-dose in each treatment period (13 samples in total)

• Time to attain maximum concentration (tmax)

  From pre-dose until 56 hours post-dose in each treatment period (13 samples in total)

• Maximum observed plasma concentration (Cmax)

  From pre-dose until 56 hours post-dose in each treatment period (13 samples in total)

Study Arms (7)

Cebranopadol 200 micrograms (Treatment A)

EXPERIMENTAL

Cebranopadol 200 micrograms (low dose): Participants took 2 tablets (cebranopadol 100 micrograms) as a single dose. In addition, participants took 4 placebo capsules matching hydromorphone capsules as a single dose.

Drug: Cebranopadol 100 micrograms; Drug: Placebo matching hydromorphone

Cebranopadol 400 micrograms (Treatment B)

EXPERIMENTAL

Cebranopadol 400 micrograms (medium dose): Participants took 2 tablets (cebranopadol 400 micrograms plus matching placebo) as a single dose. In addition, participants took 4 placebo capsules matching hydromorphone capsules as a single dose.

Drug: Cebranopadol 400 micrograms; Drug: Placebo matching hydromorphone

Cebranopadol 800 micrograms (Treatment C)

EXPERIMENTAL

Cebranopadol 800 micrograms (high dose): Participants took 2 tablets containing cebranopadol 400 micrograms as a single dose. In addition, participants took 4 placebo capsules matching hydromorphone capsules as a single dose.

Drug: Cebranopadol 400 micrograms; Drug: Placebo matching hydromorphone

Hydromorphone IR 8 milligrams (Treatment D)

ACTIVE COMPARATOR

Hydromorphone immediate-release (IR) 8 milligrams: Participants took 4 capsules (2 capsules of hydromorphone hydrochloride 4 mg plus 2 placebo capsules) as a single dose. In addition, participants took 2 placebo tablets matching cebranopadol tablets as a single dose.

Drug: Hydromorphone hydrochloride 4 milligrams; Drug: Placebo matching cebranopadol

Hydromorphone IR 16 milligrams (Treatment E)

ACTIVE COMPARATOR

Hydromorphone immediate-release (IR) 16 milligrams: Participants took 4 capsules of hydromorphone hydrochloride 4 mg as a single dose. In addition, participants took 2 placebo tablets matching cebranopadol tablets as a single dose.

Drug: Hydromorphone hydrochloride 4 milligrams; Drug: Placebo matching cebranopadol

Placebo (Treatment F)

PLACEBO COMPARATOR

Placebo: Participants took 4 placebo capsules matching hydromorphone capsules as a single dose. In addition, participants took 2 placebo tablets matching cebranopadol tablets as a single dose.

Drug: Placebo matching hydromorphone; Drug: Placebo matching cebranopadol

Placebo (Treatment G)

PLACEBO COMPARATOR

Placebo (following Treatment C): Participants took 2 placebo tablets matching cebranopadol tablets as a single dose. In addition, participants took 4 placebo capsules matching hydromorphone capsules as a single dose.

Drug: Placebo matching hydromorphone; Drug: Placebo matching cebranopadol

Interventions

Cebranopadol 100 micrograms DRUG

Tablets were taken under fasted conditions with non-carbonated water.

Cebranopadol 200 micrograms (Treatment A)

Cebranopadol 400 micrograms DRUG

Tablets were taken under fasted conditions with non-carbonated water.

Cebranopadol 400 micrograms (Treatment B); Cebranopadol 800 micrograms (Treatment C)

Hydromorphone hydrochloride 4 milligrams DRUG

Over-encapsulated immediate-release tablets were taken under fasted conditions with non-carbonated water.

Also known as: Dilaudid (Trade Mark) 4 mg

Hydromorphone IR 16 milligrams (Treatment E); Hydromorphone IR 8 milligrams (Treatment D)

Placebo matching hydromorphone DRUG

Placebo matching over-encapsulated hydromorphone tablets were taken under fasted conditions with non-carbonated water.

Cebranopadol 200 micrograms (Treatment A); Cebranopadol 400 micrograms (Treatment B); Cebranopadol 800 micrograms (Treatment C); Placebo (Treatment F); Placebo (Treatment G)

Placebo matching cebranopadol DRUG

Placebo matching cebranopadol tablets were taken under fasted conditions with non-carbonated water.

Hydromorphone IR 16 milligrams (Treatment E); Hydromorphone IR 8 milligrams (Treatment D); Placebo (Treatment F); Placebo (Treatment G)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Informed consent signed.
• Male and female, aged 18 years to 55 years, inclusive.
• History of recreational opioid use (defined as non-therapeutic use at least 10 times in the participant's lifetime and at least once in the last 12 weeks prior to the Enrollment Visit).
• Body mass index between 19 kilograms per square meter and 32 kilograms per square meter inclusive, with a body weight of not less than 50 kilograms at enrollment.
• Participants must be in good health as determined by medical history, physical examination, 12-lead electrocardiogram (ECG), and vital signs (pulse rate, systolic blood pressure and diastolic blood pressure, respiratory rate, and oxygen saturation using pulse oximetry) at enrollment.
• Adequate contraception is being used or women of non-childbearing potential may be enrolled if surgically sterile (i.e., after hysterectomy) or post-menopausal for at least 2 years (based on participant's report).
• For women of childbearing potential: A medically acceptable and highly effective method of birth control is defined as any form of contraception with a low failure rate defined as less than 1 percent per year. For example:
• Hormonal contraceptives for at least 8 weeks prior to the Enrollment Visit and at least until 4 weeks after the Final Examination.
• An intra-uterine device. Additional barrier contraception should be used by the partner for the duration of the study, defined as from the time of the Enrollment Visit until 4 weeks after the Final Examination. A single barrier method alone is not acceptable.
• For men: Participants must be willing to use medically acceptable and highly effective methods of birth control. Participants must be willing to use barrier contraception (condom) during sexual intercourse with females from the first administration of investigational medicinal product (IMP) until 4 weeks after the Final Examination. Participants must be willing to take care that their female sexual partner uses at least 1 additional method of contraception with a low failure rate defined as less than 1 percent per year (e.g., hormonal contraceptives, diaphragm) during this time frame. A single barrier method alone is not acceptable.

You may not qualify if:

• Current substance dependence (except nicotine and caffeine dependence) as defined by the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV).
• Unwillingness or inability to abstain from recreational drug use for the duration of the study.
• Positive or missing alcohol breath test at enrollment.
• Participants attempting to discontinue their recreational drug use or who had been in a drug rehabilitation program in the 12 months prior to enrollment.
• Current consumption of more than 20 cigarettes per day or inability to abstain from smoking (or use of any nicotine-containing substance) for at least 26 hours.
• Participation in another clinical study within 30 days prior to enrollment that resulted in the administration of at least 1 dose of IMP.
• Diseases or conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• Prolongation of corrected QT interval (Fridericia) (QTcF) (after repeated assessment) at enrollment, i.e., above 450 milliseconds, or presence of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia), or use of concomitant medications that prolong QT interval.
• History of orthostatic hypotension or other cardiovascular diseases.
• Any clinically significant disease that in the investigator's opinion may affect efficacy or safety assessments or may compromise the participant's safety during study participation, e.g., significant pulmonary, gastrointestinal, cardiac, endocrine, metabolic, neurological, or psychiatric disorders.
• Definite or suspected history of drug allergy or hypersensitivity to opioids or naloxone.
• Use of forbidden medication within 2 weeks prior to enrollment into this study.
• Any contraindication for naloxone or hydromorphone immediate-release (IR) administration.
• Not able to abstain from consumption of:
• Beverages or food containing caffeine (tea, coffee, cola, chocolate, etc.) or alcohol from 2 days prior to each Day 1 until discharge from the ward.

Sponsors & Collaborators

• Tris Pharma, Inc.: lead

Study Sites (1)

INC Research

Toronto, Ontario, M5V 2T3, Canada

Location

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

Hydromorphone

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphine Derivatives; 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 Officials

• Grünenthal Study Director

  Grünenthal GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Nested-randomized, single site, double-blind, double-dummy, placebo- and active-controlled, crossover design with administration of a single oral dose. Based on the assigned treatment sequence, each participant was randomly allocated to receive a single oral dose of the investigational medicinal product (IMP) in each of 7 periods. One administration of placebo (Treatment G) always followed cebranopadol 800 micrograms (Treatment C). Each IMP administration was given under fasted conditions and was separated by a washout period of at least 14 days.

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: November 29, 2018
• Study Start: April 15, 2013
• Primary Completion: March 8, 2014
• Study Completion: March 8, 2014
• Last Updated: July 15, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)