Study to Evaluate Drug-drug Interactions of Guaifenesin and Hydrocodone Bitartrate

NCT03642873 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 2006-HYDRO-04
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Determine and compare the plasma concentrations and safety and tolerability of Guaifenesin and hydrocodone bitartrate when they are administered alone or in combination to normal healthy male and/or female subjects.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (6)

• Maximum Observed Plasma Concentration (Cmax) of Guaifenesin

  Pharmacokinetic Parameter Cmax (Maximum measured plasma concentration)

  0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 8.5, 9, 9.5, 10, 11, 13, 16, 20, 24, and 26 hours Post dose

• Area Under Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUC(0-t)) of Guaifenesin

  Pharmacokinetic Parameter AUC(0-t) The area under the plasma concentration versus time curve from time 0 to time of the last measurable concentration.

  0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 8.5, 9, 9.5, 10, 11, 13, 16, 20, 24, and 26 hours Post dose

• Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUC(0-inf)) of Guaifenesin

  The area under the plasma concentration versus time curve from time 0 to infinity, calculated as AUC(0-t) + Ct/ Kel, where Ct is the last measurable concentration.

  0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 8.5, 9, 9.5, 10, 11, 13, 16, 20, 24, and 26 hours Post dose

• Apparent Terminal Elimination Rate Constant (Kel) of Guaifenesin

  Apparent first-order terminal elimination rate constant calculated from a semi-log plot of the plasma concentration versus time curve. The parameter was calculated by linear least-squares regression analysis using the maximum number of points in the terminal log-linear phase.

  0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 8.5, 9, 9.5, 10, 11, 13, 16, 20, 24, and 26 hours Post dose

• Time to Maximum Observed Concentration (Tmax) of Guaifenesin

  Pharmacokinetic Parameter (Tmax) Time of the maximum measured plasma concentration.

  0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 8.5, 9, 9.5, 10, 11, 13, 16, 20, 24, and 26 hours Post dose

• Apparent Terminal Elimination Half-life (T1/2) of Guaifenesin

  Apparent first-order terminal elimination half-life was calculated as 0.693/Kel.

  0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 8.5, 9, 9.5, 10, 11, 13, 16, 20, 24, and 26 hours Post dose

Secondary Outcomes (1)

• Number of Adverse Events(AEs) Experienced by Participants

  Upto Day 17

Study Arms (3)

Treatment A

EXPERIMENTAL

Guaifenesin (Humibid®) single extended release 1200 mg tablet administered with 240 mL of room temperature water under fasted conditions.

Drug: Humibid®

Treatment B

EXPERIMENTAL

Hydrocodone Bitartrate of 10 mg in 3 oral doses of a single 3.33 mg tablet in three intervals administered with 240 mL of room temperature water in the fasted state.

Drug: Hydrocodone Bitartrate

Treatment C

EXPERIMENTAL

Hydrocodone Bitartrate 10 mg in 3 oral doses of a single 3.33 mg tablet in three intervals and guaifenesin (Humibid®) 1200 mg ER administered with 240 mL of room temperature water in the fasted state.

Drug: Humibid® and Hydrocodone Bitartrate tablet

Interventions

Humibid® DRUG

Humibid® 1200 mg (single extended release) tablet

Also known as: Guaifenesin

Treatment A

Hydrocodone Bitartrate DRUG

Hydrocodone Bitartrate (3.33 mg q4h X 3)

Treatment B

Humibid® and Hydrocodone Bitartrate tablet DRUG

Humibid® 1200 mg (single extended release) tablet and Hydrocodone bitartrate (3.33 mg q4h X 3)

Treatment C

Eligibility Criteria

• Age: 19 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and/or females between the ages of 19 and 55 years, inclusive.
• Females of childbearing potential were using one of the following acceptable birth control methods:
• Intrauterine device (IUD) in place for at least 3 months prior to study;
• Barrier method (condom or diaphragm) with spermicide for at least 14 days prior to screening through 30 days beyond study completion;
• Stable hormonal contraceptive for at least 3 months prior to study through 30 days beyond completion of study;
• Abstinence was not an acceptable form of contraception.
• Females of non-childbearing potential were surgically sterile (bilateral tubal ligation with surgery at least 6 months prior to study, hysterectomy, or bilateral oophorectomy at least 3 months prior to study) or postmenopausal \<2 years. An FSH \>40 mIU/mL was obtained and in the record.
• Good general health was determined by medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measures.
• Within 15% of Ideal Body Weight as defined by the 1983 Metropolitan Life chart.
• Non-tobacco users, who had not used nicotine or nicotine-containing products for at least 1 year.
• Able to read, understand, and sign the informed consent after the nature of the study had been explained.
• Negative finding on tests for Hepatitis B and C antigen as well as HIV and pregnancy test (if female).
• Negative urine screen for drugs of abuse and alcohol at screening and the first check in.
• Non-alcohol or drug abuser - for alcohol, defined as history of less then 4 drinks daily.

You may not qualify if:

• Clinically significant abnormalities detected by medical history, physical, ECG, or clinical laboratory findings (as determined by the Principal Investigator). Any disease or condition which impacted absorption, distribution, metabolism, or elimination of the study drugs.
• Females who were pregnant or nursing.
• History of hypersensitivity reaction to the study drugs or related compounds, such as other opioids.
• Receipt of an investigational drug within 1 month prior to study enrollment.
• Donation of blood or significant loss of blood within 56 days or plasma within 14 days prior study enrollment.
• Known or suspected use of illicit drugs (including codeine or hydrocodone, etc.).
• The use of any medication on a chronic basis with the exception of oral contraceptives for women of childbearing potential. An appropriate drug-free period for prescription or over-the-counter (OTC) drugs provided to washout any especially long half-life drugs.
• Consumption of alcohol within 48 hours prior to each dosing period.
• Consumption of grapefruit 14 days prior to dosing and throughout the study.
• Hemoglobin value \< 12 g/dL. If a subject's hemoglobin dropped below 11.0 g/dL the subject was dropped from the study at the Principal Investigator's discretion.

Sponsors & Collaborators

• Reckitt Benckiser LLC: lead

MeSH Terms

Interventions

Guaifenesin; Hydrocodone

Intervention Hierarchy (Ancestors)

Guaiacol; Methyl Ethers; Ethers; Organic Chemicals; Phenyl Ethers; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; 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

Results Point of Contact

• Title: Clinical Research Director, Clinical Research
• Organization: Reckitt Benckiser, Inc

clinicalrequests@rb.com

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: August 22, 2018
• Study Start: May 5, 2007
• Primary Completion: May 21, 2007
• Study Completion: May 21, 2007
• Last Updated: June 20, 2019
• Results First Posted: June 20, 2019

Record last verified: 2019-03