ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03137030
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03137030
Recruitment Status : Withdrawn (program discontinued)
First Posted : May 2, 2017
Last Update Posted : July 21, 2017
Sponsor:
Information provided by (Responsible Party):
Grünenthal GmbH

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.


Condition or disease Intervention/treatment Phase
Opioid-Related Disorders Pain, Acute Pain, Postoperative Drug: GRT7014 - Abuse Deterrend Tablet Drug: Norco 5Mg-325Mg Tablet Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Relative Bioavailability Trial to Investigate the Pharmacokinetics of Different Amounts of Tablets of Two Immediate Release Fixed Dose Combinations of Hydrocodone Bitartrate 5 mg/Acetaminophen 325 mg (a New Abuse Deterrent Tablet and a Marketed Tablet) Under Fasted Conditions in Healthy Male and Female Adult Subjects
Estimated Study Start Date : September 2017
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : January 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GRT7014 - 1 Tablet (Part 1)

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
Single oral dose in one of the four cross-over trial periods and in the standard cross-over trial periods.
Other Name: Hydrocodone bitartrate and acetaminophen

Experimental: GRT7014 - 10 Tablets (Part 1)

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
Single oral dose in one of the four cross-over trial periods and in the standard cross-over trial periods.
Other Name: Hydrocodone bitartrate and acetaminophen

Active Comparator: Norco - 1 Tablet (Part 1)
Norco fixed dose combination hydrocodone bitartrate 5 mg/acetaminophen 325 mg immediate release (IR) tablet (Norco 5Mg-325Mg Tablet).
Drug: Norco 5Mg-325Mg Tablet
Single oral dose in one of the four cross-over trial periods and in the standard cross-over trial periods.
Other Name: Hydrocodone bitartrate and acetaminophen

Active Comparator: Norco - 10 Tablets (Part 1)
Norco fixed dose combination hydrocodone bitartrate 5 mg/acetaminophen 325 mg immediate release (IR) tablet (Norco 5Mg-325Mg Tablet).
Drug: Norco 5Mg-325Mg Tablet
Single oral dose in one of the four cross-over trial periods and in the standard cross-over trial periods.
Other Name: Hydrocodone bitartrate and acetaminophen

Experimental: GRT7014 - 5 Tablets (Optional Part 2)

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
Single oral dose in one of the four cross-over trial periods and in the standard cross-over trial periods.
Other Name: Hydrocodone bitartrate and acetaminophen

Active Comparator: Norco - 5 Tablets (Optional Part 2)
Norco fixed dose combination hydrocodone bitartrate 5 mg/acetaminophen 325 mg immediate release (IR) tablet (Norco 5Mg-325Mg Tablet).
Drug: Norco 5Mg-325Mg Tablet
Single oral dose in one of the four cross-over trial periods and in the standard cross-over trial periods.
Other Name: Hydrocodone bitartrate and acetaminophen




Primary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) GRT7014 (1 and 10 Tablets) [ Time Frame: Between 0 hours and 72 hours ]
    The maximum plasma concentration of hydrocodone and of acetaminophen.

  2. Area under the plasma concentration curve from timepoint 0 to t (AUC0-t) GRT7014 (1 and 10 Tablets) [ Time Frame: Between 0 hours and 72 hours ]
    The area under the plasma concentration curve of hydrocodone and of acetaminophen.

  3. Area under the plasma concentration curve from timepoint 0 to infinity (AUC) GRT7014 (1 and 10 Tablets) [ Time Frame: Between 0 hours and 72 hours ]
    The area under the plasma concentration curve of hydrocodone and of acetaminophen.


Secondary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) GRT7014 and Norco (1, 5 (optional) and 10 Tablets) [ Time Frame: Between 0 hours and 72 hours ]
    The maximum plasma concentration of hydrocodone and of acetaminophen.

  2. Area under the plasma concentration curve from timepoint 0 to t (AUC0-t) GRT7014 and Norco (1, 5 (optional) and 10 Tablets) [ Time Frame: Between 0 hours and 72 hours ]
    The area under the plasma concentration curve of hydrocodone and of acetaminophen.

  3. Area under the plasma concentration curve from timepoint 0 to infinity (AUC) GRT7014 and Norco (1, 5 (optional) and 10 Tablets) [ Time Frame: Between 0 hours and 72 hours ]
    The area under the plasma concentration curve of hydrocodone and of acetaminophen.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
    • Exclusion range met for urinalysis or lactate dehydrogenase, potassium, total protein, sodium, calcium, hemoglobin, hematocrit, white blood cell count, or platelets.
    • 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.
  • Diseases or conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
  • History of orthostatic hypotension.
  • History of, or at risk of seizures (i.e., head trauma, epilepsy in family history, unclear loss of consciousness).
  • Definite or suspected hypersensitivity to the active substance or to any of the excipients of the IMP; especially known hypersensitivity/intolerance or contraindications to opioids, opioid antagonists, acetaminophen or any excipients of the drug formulation.
  • Evidence or history of alcohol or drug abuse including positive or missing alcohol breath test or drugs of abuse test.
  • Unable to abstain from regular use of any medication, including herbal remedies or over-the-counter medication within 2 weeks prior to the Enrollment Visit and anticipated use during the course of the trial, excluding oral contraceptives in women of childbearing potential and topical medications or nasal sprays without systemic effect.
  • Lactating or breastfeeding women.
  • Habitually smoking more than 10 cigarettes, 2 cigars, or 2 pipes of tobacco per day within the last 6 months before enrollment in this trial.
  • Unable to refrain from smoking during the stay at the trial site in each treatment period.
  • Not willing or able to abstain from consumption of:

    • Beverages or food containing methylxanthines (tea, coffee, cola, chocolate, etc.) from 48 hours prior to the planned first administration of IMP until discharge from the trial site in each treatment period.
    • Beverages or food containing quinine (bitter lemon, tonic water), grapefruit juice (sweet or sour), Seville oranges, or alcohol from 72 hours prior to the planned first administration of IMP until discharge from the trial site in each treatment period.
  • Known or suspected of not being able to comply with the requirements of the trial protocol or the instructions of the trial site staff.
  • Not able to communicate meaningfully with the trial site staff.
  • Employee of the investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site, as well as family members of the employees or the investigator.
  • Blood loss of 500 mL or more within 45 days before enrollment in this trial.
  • Unable to establish reliable venous access.
  • Medical history of bronchial asthma, Addison's disease, prostatic hypertrophy, or urethral stricture.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03137030


Locations
United States, Kansas
US001: PRA Health Sciences
Lenexa, Kansas, United States, 66219
Sponsors and Collaborators
Grünenthal GmbH
Investigators
Study Director: Grünenthal Study Director Grünenthal GmbH

Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT03137030     History of Changes
Other Study ID Numbers: HP7014-02
U1111-1184-8922 ( Other Identifier: World Health Organization )
First Posted: May 2, 2017    Key Record Dates
Last Update Posted: July 21, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:

Details available at:

http://www.grunenthal.com/grt-web/Grunenthal_Group/Research_Development/Grunenthal_Clinical_Trials/Data_Sharing/296200025.jsp


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Grünenthal GmbH:
Abuse deterrent formulation
Hydrocodone
Analgesics, Opioid
Narcotics

Additional relevant MeSH terms:
Pain, Postoperative
Opioid-Related Disorders
Acute Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Postoperative Complications
Pathologic Processes
Signs and Symptoms
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Acetaminophen
Acetaminophen, hydrocodone drug combination
Hydrocodone
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents
Anti-Inflammatory Agents, Non-Steroidal
Anti-Inflammatory Agents
Antirheumatic Agents