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

• Sponsor: Reckitt Benckiser LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03642873
• Collaborator: (none)
• Enrollment: 24
• Arms: 3
• Actual Duration (Days): 16

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects	Drug: Humibid®; Drug: Hydrocodone Bitartrate; Drug: Humibid® and Hydrocodone Bitartrate tablet	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Study Designed to Examine the Potential for a Drug-drug Interaction Between Guaifenesin and Hydrocodone Bitartrate in Normal Healthy Volunteers
• Actual Study Start Date: May 5, 2007
• Actual Primary Completion Date: May 21, 2007
• Actual Study Completion Date: May 21, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment A Guaifenesin (Humibid®) single extended release 1200 mg tablet administered with 240 mL of room temperature water under fasted conditions.	Drug: Humibid®; Humibid® 1200 mg (single extended release) tablet; Other Names: Guaifenesin
Experimental: Treatment B 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; Hydrocodone Bitartrate (3.33 mg q4h X 3)
Experimental: Treatment C 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; Humibid® 1200 mg (single extended release) tablet and Hydrocodone bitartrate (3.33 mg q4h X 3)

Outcome Measures

Primary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) of Guaifenesin [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]

   Pharmacokinetic Parameter Cmax (Maximum measured plasma concentration)

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

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

3. Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUC(0-inf)) of Guaifenesin [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]

   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.

4. Apparent Terminal Elimination Rate Constant (Kel) of Guaifenesin [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 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.

5. Time to Maximum Observed Concentration (Tmax) of Guaifenesin [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]

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

6. Apparent Terminal Elimination Half-life (T1/2) of Guaifenesin [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 first-order terminal elimination half-life was calculated as 0.693/Kel.

Secondary Outcome Measures

1. Number of Adverse Events(AEs) Experienced by Participants [Upto Day 17]

   Intensity was determined by the Investigator. For symptomatic AEs the following definitions were applied. Mild = AE did not limit usual activities; subject may have experienced slight discomfort. Moderate = AE resulted in some limitation of usual activities; subject may have experienced significant discomfort. Severe = AE resulted in an inability to carry out usual activities; subject may have experienced intolerable discomfort/ pain. Relationship to Investigational Medicinal Products (IMP) Unlikely = Slight, but remote, chance that AE was caused by IMP. Possible = Reasonable suspicion that the AE was caused by IMP. Probable = Most likely that AE was caused by IMP.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

1. Good general health was determined by medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measures.

2. Within 15% of Ideal Body Weight as defined by the 1983 Metropolitan Life chart.

3. Non-tobacco users, who had not used nicotine or nicotine-containing products for at least 1 year.

4. Able to read, understand, and sign the informed consent after the nature of the study had been explained.

5. Negative finding on tests for Hepatitis B and C antigen as well as HIV and pregnancy test (if female).

6. Negative urine screen for drugs of abuse and alcohol at screening and the first check in.

7. 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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Reckitt Benckiser LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Reckitt Benckiser LLC
• ClinicalTrials.gov Identifier: NCT03642873
• Other Study ID Numbers: 2006-HYDRO-04
• First Posted: Aug 22, 2018
• Last Update Posted: Jun 20, 2019
• Last Verified: Mar 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Phenylpropanolamine; Hydrocodone; Guaifenesin; Chlorpheniramine, phenylpropanolamine drug combination

Study Results

Participant Flow

Recruitment Details	This was a single-centre study.
Pre-assignment Detail	A total of 24 subjects entered the study, among them 23 subjects completed the study.

Arm/Group Title	Sequence ABC	Sequence ACB	Sequence BAC	Sequence BCA	Sequence CAB	Sequence CBA
Arm/Group Description	First Intervention Treatment A: Single Humibid® 1200 mg guaifenesin Extended Release (ER) bi-layer tablet by mouth under fasted state Second Intervention Treatment B: Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Third Intervention Treatment C: Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Scheduled Washout of 7 days between each doses.	First Intervention Treatment A: Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state Second Intervention Treatment C: Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Third Intervention Treatment B: Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Scheduled Washout of 7 days between each doses.	First Intervention Treatment B: Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Second Intervention Treatment A: Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state Third Intervention Treatment C: Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Scheduled Washout of 7 days between each doses.	First Intervention Treatment B: Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Second Intervention Treatment C: Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Third Intervention Treatment A: Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state Scheduled Washout of 7 days between each doses.	First Intervention Treatment C: Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Second Intervention Treatment A: Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state Third Intervention Treatment B: Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Scheduled Washout of 7 days between each doses.	First Intervention Treatment C: Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Second Intervention Treatment B: Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Third Intervention Treatment A: Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state Scheduled Washout of 7 days between each doses.
Period Title: First Intervention (1 Day)
STARTED	4	4	4	4	4	4
COMPLETED	4	4	4	4	4	4
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention (1 Day)
STARTED	4	4	4	4	4	4
COMPLETED	4	4	4	4	4	4
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention (1 Day)
STARTED	4	4	4	4	4	4
COMPLETED	4	4	4	4	4	4
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention (1 Day)
STARTED	4	4	4	4	4	4
COMPLETED	4	4	4	4	4	4
NOT COMPLETED	0	0	0	0	0	0
Period Title: First Intervention (1 Day)
STARTED	4	4	4	4	4	4
COMPLETED	4	4	4	4	3	4
NOT COMPLETED	0	0	0	0	1	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Participants were randomized at each visit to receive either Treatment A (Reference): Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state Treatment B (Reference): Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Treatment C (Test): Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state Scheduled Washout of 7 days between each doses. All study participants received all three treatments
Overall Participants	24
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	29.6 (9.2)
Sex: Female, Male (Count of Participants)
Female	14 58.3%
Male	10 41.7%
Race/Ethnicity, Customized (Count of Participants)
American Indian	1 4.2%
Asian	1 4.2%
Black	2 8.3%
Caucasian	17 70.8%
Hispanic	3 12.5%
Weight (lb) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [lb]	148.3 (18.8)
Height (Inches) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Inches]	67.5 (3.3)
Elbow Breadth (Inches) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Inches]	2.6 (0.2)
Frame Size (participants) [Number]
Small	7 29.2%
Medium	15 62.5%
Large	2 8.3%

Outcome Measures

1. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Guaifenesin
Description	Pharmacokinetic Parameter Cmax (Maximum measured plasma concentration)
Time Frame	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Data Sets included all the 24 subjects for analysis.

Arm/Group Title	Treatment A (Reference) - Plasma Guaifenesin	Treatment C (Test) - Plasma Guaifenesin	Treatments B (Reference) - Plasma Hydrocodone Bitartrate	Treatment C (Test) - Plasma Hydrocodone Bitartrate
Arm/Group Description	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state.	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.	Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.
Measure Participants	24	24	23	24
Mean (Standard Deviation) [ng/mL]	1770 (628)	1810 (784)	11.3 (2.14)	11.3 (1.78)

2. Primary Outcome

Title	Area Under Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUC(0-t)) of Guaifenesin
Description	Pharmacokinetic Parameter AUC(0-t) The area under the plasma concentration versus time curve from time 0 to time of the last measurable concentration.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Data Sets

Arm/Group Title	Treatment A (Reference) - Plasma Guaifenesin	Treatment C (Test) - Plasma Guaifenesin	Treatments B (Reference) - Plasma Hydrocodone Bitartrate	Treatment C (Test) - Plasma Hydrocodone Bitartrate
Arm/Group Description	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state.	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.	Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.
Measure Participants	24	24	23	24
Mean (Standard Deviation) [ng*hr/mL]	8286.2 (2440.0)	8186.7 (2801.0)	133.36 (29.407)	132.99 (23.053)

3. Primary Outcome

Title	Area Under Plasma Concentration-time Curve From Time 0 to Infinity (AUC(0-inf)) of Guaifenesin
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Data Sets

Arm/Group Title	Treatment A (Reference) - Plasma Guaifenesin	Treatment C (Test) - Plasma Guaifenesin	Treatments B (Reference) - Plasma Hydrocodone Bitartrate	Treatment C (Test) - Plasma Hydrocodone Bitartrate
Arm/Group Description	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state.	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.	Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.
Measure Participants	20	21	23	24
Mean (Standard Deviation) [ng*hr/mL]	8501.5 (2784.5)	8347.8 (2762.4)	140.44 (32.792)	139.70 (26.044)

4. Primary Outcome

Title	Apparent Terminal Elimination Rate Constant (Kel) of Guaifenesin
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Data Sets

Arm/Group Title	Treatment A (Reference) - Plasma Guaifenesin	Treatment C (Test) - Plasma Guaifenesin	Treatments B (Reference) - Plasma Hydrocodone Bitartrate	Treatment C (Test) - Plasma Hydrocodone Bitartrate
Arm/Group Description	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state.	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.	Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.
Measure Participants	20	21	23	24
Mean (Standard Deviation) [1/hr]	0.205 (0.104)	0.207 (0.199)	0.151 (0.0251)	0.155 (0.0233)

5. Primary Outcome

Title	Time to Maximum Observed Concentration (Tmax) of Guaifenesin
Description	Pharmacokinetic Parameter (Tmax) Time of the maximum measured plasma concentration.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Data Sets

Arm/Group Title	Treatment A (Reference) - Plasma Guaifenesin	Treatment C (Test) - Plasma Guaifenesin	Treatments B (Reference) - Plasma Hydrocodone Bitartrate	Treatment C (Test) - Plasma Hydrocodone Bitartrate
Arm/Group Description	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state.	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.	Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.
Measure Participants	24	24	23	24
Mean (Standard Deviation) [hr]	1.08 (0.551)	1.04 (0.415)	9.59 (2.16)	9.33 (2.09)

6. Primary Outcome

Title	Apparent Terminal Elimination Half-life (T1/2) of Guaifenesin
Description	Apparent first-order terminal elimination half-life was calculated as 0.693/Kel.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Data Sets

Arm/Group Title	Treatment A (Reference) - Plasma Guaifenesin	Treatment C (Test) - Plasma Guaifenesin	Treatments B (Reference) - Plasma Hydrocodone Bitartrate	Treatment C (Test) - Plasma Hydrocodone Bitartrate
Arm/Group Description	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state.	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.	Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state.
Measure Participants	20	21	23	24
Mean (Standard Deviation) [hr]	4.82 (3.30)	5.34 (3.13)	4.71 (0.833)	4.60 (0.831)

7. Secondary Outcome

Title	Number of Adverse Events(AEs) Experienced by Participants
Description	Intensity was determined by the Investigator. For symptomatic AEs the following definitions were applied. Mild = AE did not limit usual activities; subject may have experienced slight discomfort. Moderate = AE resulted in some limitation of usual activities; subject may have experienced significant discomfort. Severe = AE resulted in an inability to carry out usual activities; subject may have experienced intolerable discomfort/ pain. Relationship to Investigational Medicinal Products (IMP) Unlikely = Slight, but remote, chance that AE was caused by IMP. Possible = Reasonable suspicion that the AE was caused by IMP. Probable = Most likely that AE was caused by IMP.
Time Frame	Upto Day 17

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Data Sets

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state	Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state
Measure Participants	24	23	24
TEAE by severity: Mild	7	12	25
TEAE by severity: Moderate	0	1	0
TEAE by severity: Severe	0	0	0
Relationship to IMP - Unlikely	4	0	1
Relationship to IMP - Possible	3	8	8
Relationship to IMP - Probable	0	5	16

Adverse Events

Time Frame	Up to Day 17
Arm/Group Title	Treatment A		Treatment B		Treatment C
Arm/Group Description	Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet by mouth under fasted state		Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state		Single Humibid® 1200 mg guaifenesin Extended-Release (ER) bi-layer tablet and Hydrocodone Bitartrate 10 mg (3.33 mg q4h X 3) tablet by mouth under fasted state
All Cause Mortality
	Treatment A		Treatment B		Treatment C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/23 (0%)		0/24 (0%)
Serious Adverse Events
	Treatment A		Treatment B		Treatment C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/23 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Treatment A		Treatment B		Treatment C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/24 (20.8%)		10/23 (43.5%)		10/24 (41.7%)
Cardiac disorders
Palpitations	0/24 (0%)	0	1/23 (4.3%)	1	0/24 (0%)	0
Eye disorders
Lacrimation increased	1/24 (4.2%)	1	0/23 (0%)	0	0/24 (0%)	0
Gastrointestinal disorders
Nausea	0/24 (0%)	0	4/23 (17.4%)	4	2/24 (8.3%)	2
Stomach discomfort	0/24 (0%)	0	0/23 (0%)	0	1/24 (4.2%)	1
General disorders
Fatigue	0/24 (0%)	0	2/23 (8.7%)	2	1/24 (4.2%)	1
Musculoskeletal and connective tissue disorders
Muscular weakness	0/24 (0%)	0	0/23 (0%)	0	1/24 (4.2%)	1
Nervous system disorders
Clumsiness	0/24 (0%)	0	0/23 (0%)	0	1/24 (4.2%)	1
Dizziness	0/24 (0%)	0	0/23 (0%)	0	6/24 (25%)	8
Head discomfort	0/24 (0%)	0	0/23 (0%)	0	1/24 (4.2%)	1
Headache	4/24 (16.7%)	4	5/23 (21.7%)	5	5/24 (20.8%)	6
Paraesthesia	0/24 (0%)	0	0/23 (0%)	0	1/24 (4.2%)	1
Tremor	0/24 (0%)	0	1/23 (4.3%)	1	1/24 (4.2%)	1
Psychiatric disorders
Euphoric mood	0/24 (0%)	0	0/23 (0%)	0	1/24 (4.2%)	1
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	1/24 (4.2%)	1	0/23 (0%)	0	0/24 (0%)	0
Sneezing	1/24 (4.2%)	1	0/23 (0%)	0	0/24 (0%)	0
Vascular disorders
Pallor	0/24 (0%)	0	0/23 (0%)	0	1/24 (4.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.