A Comparison of Plasma Concentrations of Hydrocodone and Acetaminophen After Administration of Different Amounts of Tablets of a New and a Marketed Tablet Formulation in Healthy Adults

NCT03137030 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: HP7014-02U1111-1184-8922
• 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 different amounts of tablets of a new and a marketed tablet formulation in healthy adults. Part 1 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. Part will consist of an Enrollment Visit, 4 treatment periods (each lasting approximately 90 hours), and a Final Examination. The treatment periods will be separated by a washout period each lasting at least 7 days. Part 2 is optional and depending on pharmacokinetic data review after Part 1. It is a randomized, single-site, open-label, 2-treatment, 2-period crossover, single oral dose part in healthy male and female subjects. Part 2 will consist of an Enrollment Visit, 2 treatment periods (each lasting approximately 90 hours) and a Final Examination. The treatment periods will be separated by a washout period lasting at least 7 days. Participants must fast for approximately 10 hours prior to administration of Investigational medicinal product (IMP) and until approximately 4 hours after the administration of the IMP.

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) GRT7014 (1 and 10 Tablets)

  The maximum plasma concentration of hydrocodone and of acetaminophen.

  Between 0 hours and 72 hours

• Area under the plasma concentration curve from timepoint 0 to t (AUC0-t) GRT7014 (1 and 10 Tablets)

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

  Between 0 hours and 72 hours

• Area under the plasma concentration curve from timepoint 0 to infinity (AUC) GRT7014 (1 and 10 Tablets)

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

  Between 0 hours and 72 hours

Secondary Outcomes (3)

• Maximum Plasma Concentration (Cmax) GRT7014 and Norco (1, 5 (optional) and 10 Tablets)

  Between 0 hours and 72 hours

• Area under the plasma concentration curve from timepoint 0 to t (AUC0-t) GRT7014 and Norco (1, 5 (optional) and 10 Tablets)

  Between 0 hours and 72 hours

• Area under the plasma concentration curve from timepoint 0 to infinity (AUC) GRT7014 and Norco (1, 5 (optional) and 10 Tablets)

  Between 0 hours and 72 hours

Study Arms (6)

GRT7014 - 1 Tablet (Part 1)

EXPERIMENTAL

Abuse deterrent formulation of a fixed dose combination of hydrocodone bitartrate 5 mg/acetaminophen 325 mg immediate release (IR) tablet. (GRT7014 - Abuse Deterrend Tablet)

Drug: GRT7014 - Abuse Deterrend Tablet

GRT7014 - 10 Tablets (Part 1)

EXPERIMENTAL

Abuse deterrent formulation of a fixed dose combination of hydrocodone bitartrate 5 mg/acetaminophen 325 mg immediate release (IR) tablet. (GRT7014 - Abuse Deterrend Tablet)

Drug: GRT7014 - Abuse Deterrend Tablet

Norco - 1 Tablet (Part 1)

ACTIVE COMPARATOR

Norco fixed dose combination hydrocodone bitartrate 5 mg/acetaminophen 325 mg immediate release (IR) tablet (Norco 5Mg-325Mg Tablet).

Drug: Norco 5Mg-325Mg Tablet

Norco - 10 Tablets (Part 1)

ACTIVE COMPARATOR

Norco fixed dose combination hydrocodone bitartrate 5 mg/acetaminophen 325 mg immediate release (IR) tablet (Norco 5Mg-325Mg Tablet).

Drug: Norco 5Mg-325Mg Tablet

GRT7014 - 5 Tablets (Optional Part 2)

EXPERIMENTAL

Abuse deterrent formulation of a fixed dose combination of hydrocodone bitartrate 5 mg/acetaminophen 325 mg immediate release (IR) tablet. (GRT7014 - Abuse Deterrend Tablet)

Drug: GRT7014 - Abuse Deterrend Tablet

Norco - 5 Tablets (Optional Part 2)

ACTIVE COMPARATOR

Norco fixed dose combination hydrocodone bitartrate 5 mg/acetaminophen 325 mg immediate release (IR) tablet (Norco 5Mg-325Mg Tablet).

Drug: Norco 5Mg-325Mg Tablet

Interventions

GRT7014 - Abuse Deterrend Tablet DRUG

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

Also known as: Hydrocodone bitartrate and acetaminophen

GRT7014 - 1 Tablet (Part 1); GRT7014 - 10 Tablets (Part 1); GRT7014 - 5 Tablets (Optional Part 2)

Norco 5Mg-325Mg Tablet DRUG

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

Also known as: Hydrocodone bitartrate and acetaminophen

Norco - 1 Tablet (Part 1); Norco - 10 Tablets (Part 1); Norco - 5 Tablets (Optional Part 2)

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 minimal 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, respiratory rate), body temperature, oxygen saturation, and safety laboratory parameters (hematology, clinical chemistry, clotting, and urinalysis).
• From the first administration of IMP until at least 4 weeks (for women)/90 days (for men) after 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 at least 90 days after 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 until at least 90 days after the Final Examination.

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.
• 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, and 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, (HBsAg), hepatitis B core antigen antibodies (anti-HBc), or hepatitis C virus antibodies.
• For women of childbearing potential only: positive or missing pregnancy test.
• Subject received IMP in another clinical trial (when assessing for Part 2, excludes IMP received in Part 1 of this 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

Hydrocodone; Acetaminophen; oxycodone-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: For Part 1, the randomization will be realized using a Williams Square with a 4x4 design. For the optional Part 2, a standard 2x2 crossover design will be applied.

Study Record Dates

• First Submitted: April 27, 2017
• First Posted: May 2, 2017
• Study Start: September 1, 2017
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: July 21, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)