Clinical trial NCT03642873: Study to Evaluate Drug-drug Interactions of Guaifenesin and Hydrocodone Bitartrate
Official title: A Study Designed to Examine the Potential for a Drug-drug Interaction Between Guaifenesin and Hydrocodone Bitartrate in Normal Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Reckitt Benckiser LLC
Sponsor class: INDUSTRY
First posted: 2018-08-22
Enrollment: 24
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: Inclusion Criteria:

1. Males and/or females between the ages of 19 and 55 years, inclusive.
2. 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.
3. Good general health was determined by medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measures.
4. Within 15% of Ideal Body Weight as defined by the 1983 Metropolitan Life chart.
5. Non-tobacco users, who had not used nicotine or nicotine-containing products for at least 1 year.
6. Able to read, understand, and sign the informed consent after the nature of the study had been explained.
7. Negative finding on tests for Hepatitis B and C antigen as well as HIV and pregnancy test (if female).
8. Negative urine screen for drugs of abuse and alcohol at screening and the first check in.
9. Non-alcohol or drug abuser - for alcohol, defined as history of less then 4 drinks daily.

Exclusion Criteria:

1. 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.
2. Females who were pregnant or nursing.
3. History of hypersensitivity reaction to the study drugs or related compounds, such as other opioids.
4. Receipt of an investigational drug within 1 month prior to study enrollment.
5. Donation of blood or significant loss of blood within 56 days or plasma within 14 days prior study enrollment.
6. Known or suspected use of illicit drugs (including codeine or hydrocodone, etc.).
7. 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.
8. Consumption of alcohol within 48 hours prior to each dosing period.
9. Consumption of grapefruit 14 days prior to dosing and throughout the study.
10. 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Guaifenesin
timeFrame: 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
measure: Area Under Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUC(0-t)) of Guaifenesin
timeFrame: 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
measure: Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUC(0-inf)) of Guaifenesin
timeFrame: 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
measure: Apparent Terminal Elimination Rate Constant (Kel) of Guaifenesin
timeFrame: 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
measure: Time to Maximum Observed Concentration (Tmax) of Guaifenesin
timeFrame: 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
measure: Apparent Terminal Elimination Half-life (T1/2) of Guaifenesin
timeFrame: 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:
measure: Number of Adverse Events(AEs) Experienced by Participants
timeFrame: Upto Day 17
Other outcomes:
Locations:
Study officials:
References: