A Comparison of Plasma Concentrations of Hydrocodone and Acetaminophen After Administration of a New and a Marketed Tablet Formulation Under Fasted and Fed Conditions in Healthy Adults

NCT03137017 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: HP7014-01U1111-1183-5343
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is being conducted to compare concentrations of hydrocodone and acetaminophen in the blood after administration of a new and a marketed tablet formulation under fasted and fed conditions in healthy adults. This is a randomized, single-site, open-label, 4-treatment, 4-period crossover, single oral dose Phase I trial in 32 healthy male and female subjects. The trial will consist of an Enrollment Visit, 4 treatment periods (each lasting approximately 60 hours) separated by 3 washout periods (each lasting at least 7 days), and a Final Examination.

Conditions

Opioid-Related Disorders; Pain, Acute; Pain, Postoperative

Keywords

Abuse deterrent formulation; Hydrocodone; Analgesics, Opioid; Narcotics

Outcome Measures

Primary Outcomes (3)

• Maximum Plasma Concentration (Cmax)

  The maximum plasma concentration of hydrocodone and of acetaminophen under fed and fasted conditions.

  Between 0 hours and 36 hours

• Area under the plasma concentration curve from timepoint 0 to t (AUC0-t)

  The area under the plasma concentration curve of hydrocodone and of acetaminophen under fed and fasted conditions.

  Between 0 hours and 36 hours

• Area under the plasma concentration curve from timepoint 0 to infinity (AUC)

  The area under the plasma concentration curve of hydrocodone and of acetaminophen under fed and fasted conditions.

  Between 0 hours and 36 hours

Study Arms (4)

GRT7014 fasted

EXPERIMENTAL

Abuse deterrent formulation of a fixed dose combination of hydrocodone bitartrate 5 mg/acetaminophen 325 mg tablet (GRT7014 - Abuse Deterrent Tablet) under fasted conditions. Participant must fast from approximately 10:00 pm pre-dosing day until 4 hours after the administration of the Investigational medicinal product (IMP).

Drug: GRT7014 - Abuse Deterrent Tablet

GRT7014 fed

EXPERIMENTAL

Abuse deterrent formulation of a fixed dose combination of hydrocodone bitartrate 5 mg/acetaminophen 325 mg tablet (GRT7014 - Abuse Deterrent Tablet) under fed conditions. Participant must fast from approximately 10:00 pm pre-dosing day until they consume a high-calorie and high-fat breakfast the following morning. The IMP must be administered as soon as the meal has been eaten.

Drug: GRT7014 - Abuse Deterrent Tablet

Norco fasted

ACTIVE COMPARATOR

Norco fixed dose combination Hydrocodone bitartrate 5 mg/acetaminophen 325 mg tablet (Norco 5Mg-325Mg Tablet) under fasted conditions. Participant must fast from approximately 10:00 pm pre-dosing day until 4 hours after the administration of the IMP.

Drug: Norco 5Mg-325Mg Tablet

Norco fed

ACTIVE COMPARATOR

Norco fixed dose combination Hydrocodone bitartrate 5 mg/acetaminophen 325 mg tablet (Norco 5Mg-325Mg Tablet) under fed conditions. Participant must fast from approximately 10:00 pm pre-dosing day until they consume a high-calorie and high-fat breakfast the following morning. The IMP must be administered as soon as the meal has been eaten.

Drug: Norco 5Mg-325Mg Tablet

Interventions

Norco 5Mg-325Mg Tablet DRUG

Single oral dose in one of the four cross-over trial periods.

Also known as: Hydrocodone bitartrate and acetaminophen

Norco fasted; Norco fed

GRT7014 - Abuse Deterrent Tablet DRUG

Single oral dose in one of the four cross-over trial periods.

Also known as: Hydrocodone bitartrate and acetaminophen

GRT7014 fasted; GRT7014 fed

Eligibility Criteria

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

You may qualify if:

• Subjects have given written informed consent to participate.
• Body mass index between 20 kg/m2 and 30 kg/m2 inclusive, with a minimum body weight of 60 kg.
• Subjects must be in good health as determined by the medical history, physical and laboratory examinations and must not show any clinically significant deviations from reference ranges as determined by 12-lead electrocardiogram (ECG), vital signs (blood pressure, pulse rate, respiration rate), body temperature, oxygen saturation, and safety laboratory parameters (hematology, clinical chemistry, clotting, and urinalysis).
• From the first administration of IMP until at least the Final Examination, subjects must agree to use highly effective contraception with a low failure rate defined as \<1% per year.
• For female subjects of childbearing potential:
• Combined (estrogen and progestogen containing) hormonal contraception.
• Progestogen-only hormonal contraception associated with inhibition of ovulation.
• An intra-uterine device (hormone-free).
• An intra-uterine hormone releasing system (IUS).
• Bilateral tubal occlusion.
• Women of non-childbearing potential may be included if surgically sterile (i.e., after hysterectomy or bilateral oophorectomy) or post-menopausal for at least 12 months (i.e., spontaneous amenorrhea at least 1 year prior to screening with confirmed follicle-stimulating hormone level \>40 IU/L).
• For male subjects:
• Male subjects have to use barrier contraception (condom) during sexual intercourse with women of childbearing potential from the first application of IMP until the Final Examination. The male subject has to be willing to ensure that the female sexual partner uses at least 1 additional method of contraception with a low failure rate defined as \<1% per year.

You may not qualify if:

• Withdrawal of informed consent.
• Received forbidden medication or an investigational medical device since the Enrollment Visit.
• Any relevant deterioration in the health of the subject since the Enrollment Visit possibly impacting participation in the trial at the discretion of the investigator, including: adverse events; vital signs (relevant out-of-reference blood pressure or pulse rate if technical failure can be excluded and result is confirmed by at least 1 additional measurement); physical examination, 12-lead ECG (relevant QTc prolongation if result is confirmed by 1 additional ECG measurement and manual re-evaluation by the investigator); other safety parameters.
• Blood loss of 100 mL or more since enrollment in this trial (excluding blood taken for this trial).
• Resting pulse rate \<50 beats per minute or \>90 beats per minute.
• Resting systolic blood pressure \<90 mmHg or \>140 mmHg. Resting diastolic blood pressure \>90 mmHg.
• Prolongation of corrected QT interval (according to Fridericia's formula; QTcF), i.e., QTcF \>450 ms or presence of other of risk factors for torsade de pointes (e.g., heart failure, hypokalemia).
• Evidence for thyroid disease based on clinical and safety laboratory findings, including thyroid stimulating hormone.
• Any laboratory value (from blood samples taken at the Enrollment Visit) meeting the following criteria:
• Out-of-reference range value for alanine transaminase, aspartate transaminase, alkaline phosphatase, total bilirubin, glucose (fasted), gamma-glutamyl transferase, serum creatinine, prothrombin time, or international normalized ratio.
• Out-of-reference range value for any other safety laboratory parameter that is judged as clinically relevant by the investigator.
• A single repeat laboratory test (for each out-of-range parameter) is allowed to rule out laboratory error.
• Positive or missing virus serology test (in blood sample taken at the Enrollment Visit) for human immunodeficiency virus Type 1 or Type 2 antibodies, hepatitis B surface antigen, or hepatitis C virus antibodies.
• For women of childbearing potential only: positive or missing pregnancy test
• Subject received IMP in another clinical trial within 30 days before the Enrollment Visit. Depending on the nature of the previous IMP, a longer washout may be needed.

Sponsors & Collaborators

• Grünenthal GmbH: lead

Study Sites (1)

US001: PRA Health Sciences

Lenexa, Kansas, 66219, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders; Acute Pain; Pain, Postoperative

Interventions

oxycodone-acetaminophen; Hydrocodone; Acetaminophen

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Pathologic Processes

Intervention Hierarchy (Ancestors)

Codeine; 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; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Grünenthal Study Director

  Grünenthal GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The randomization will be realized using a Williams Square with a 4x4 design.

Study Record Dates

• First Submitted: April 27, 2017
• First Posted: May 2, 2017
• Study Start: September 1, 2017
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: July 21, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)