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

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: NCT03642873
Recruitment Status : Completed
First Posted : August 22, 2018
Results First Posted : June 20, 2019
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
Reckitt Benckiser LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Supportive Care
Condition Healthy Subjects
Interventions Drug: Humibid®
Drug: Hydrocodone Bitartrate
Drug: Humibid® and Hydrocodone Bitartrate tablet
Enrollment 24
Recruitment Details This was a single-centre study.
Pre-assignment Details 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
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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: Washout (7 Days)
Started 4 4 4 4 4 4
Completed 4 4 4 4 4 4
Not Completed 0 0 0 0 0 0
Period Title: Second 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: Washout (7 Days)
Started 4 4 4 4 4 4
Completed 4 4 4 4 4 4
Not Completed 0 0 0 0 0 0
Period Title: Third 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
Reason Not Completed
Screen failure             0             0             0             0             1             0
Arm/Group Title All Study Participants
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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 Number of Baseline Participants 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants
29.6  (9.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
14
  58.3%
Male
10
  41.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
American Indian
1
   4.2%
Asian
1
   4.2%
Black
2
   8.3%
Caucasian
17
  70.8%
Hispanic
3
  12.5%
Weight  
Mean (Standard Deviation)
Unit of measure:  Lb
Number Analyzed 24 participants
148.3  (18.8)
Height  
Mean (Standard Deviation)
Unit of measure:  Inches
Number Analyzed 24 participants
67.5  (3.3)
Elbow Breadth  
Mean (Standard Deviation)
Unit of measure:  Inches
Number Analyzed 24 participants
2.6  (0.2)
Frame Size  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 24 participants
Small 7
Medium 15
Large 2
1.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of Guaifenesin
Hide 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
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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
Hide 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.
Overall Number of Participants Analyzed 24 24 23 24
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
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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
Hide 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.
Overall Number of Participants Analyzed 24 24 23 24
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
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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
Hide 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.
Overall Number of Participants Analyzed 20 21 23 24
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
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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
Hide 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.
Overall Number of Participants Analyzed 20 21 23 24
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 24 24 23 24
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
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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
Hide 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.
Overall Number of Participants Analyzed 20 21 23 24
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
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Pharmacokinetic (PK) Data Sets
Arm/Group Title Treatment A Treatment B Treatment C
Hide 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
Overall Number of Participants Analyzed 24 23 24
Measure Type: Number
Unit of Measure: Events
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
Time Frame Up to Day 17
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment A Treatment B Treatment C
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)      0/23 (0.00%)      0/24 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment A Treatment B Treatment C
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/24 (0.00%)      0/23 (0.00%)      0/24 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment A Treatment B Treatment C
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/24 (20.83%)      10/23 (43.48%)      10/24 (41.67%)    
Cardiac disorders       
Palpitations  1  0/24 (0.00%)  0 1/23 (4.35%)  1 0/24 (0.00%)  0
Eye disorders       
Lacrimation increased  1  1/24 (4.17%)  1 0/23 (0.00%)  0 0/24 (0.00%)  0
Gastrointestinal disorders       
Nausea  1  0/24 (0.00%)  0 4/23 (17.39%)  4 2/24 (8.33%)  2
Stomach discomfort  1  0/24 (0.00%)  0 0/23 (0.00%)  0 1/24 (4.17%)  1
General disorders       
Fatigue  1  0/24 (0.00%)  0 2/23 (8.70%)  2 1/24 (4.17%)  1
Musculoskeletal and connective tissue disorders       
Muscular weakness  1  0/24 (0.00%)  0 0/23 (0.00%)  0 1/24 (4.17%)  1
Nervous system disorders       
Clumsiness  1  0/24 (0.00%)  0 0/23 (0.00%)  0 1/24 (4.17%)  1
Dizziness  1  0/24 (0.00%)  0 0/23 (0.00%)  0 6/24 (25.00%)  8
Head discomfort  1  0/24 (0.00%)  0 0/23 (0.00%)  0 1/24 (4.17%)  1
Headache  1  4/24 (16.67%)  4 5/23 (21.74%)  5 5/24 (20.83%)  6
Paraesthesia  1  0/24 (0.00%)  0 0/23 (0.00%)  0 1/24 (4.17%)  1
Tremor  1  0/24 (0.00%)  0 1/23 (4.35%)  1 1/24 (4.17%)  1
Psychiatric disorders       
Euphoric mood  1  0/24 (0.00%)  0 0/23 (0.00%)  0 1/24 (4.17%)  1
Respiratory, thoracic and mediastinal disorders       
Rhinorrhoea  1  1/24 (4.17%)  1 0/23 (0.00%)  0 0/24 (0.00%)  0
Sneezing  1  1/24 (4.17%)  1 0/23 (0.00%)  0 0/24 (0.00%)  0
Vascular disorders       
Pallor  1  0/24 (0.00%)  0 0/23 (0.00%)  0 1/24 (4.17%)  1
1
Term from vocabulary, MedDRA 9.1
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Research Director, Clinical Research
Organization: Reckitt Benckiser, Inc
EMail: clinicalrequests@rb.com
Layout table for additonal information
Responsible Party: Reckitt Benckiser LLC
ClinicalTrials.gov Identifier: NCT03642873     History of Changes
Other Study ID Numbers: 2006-HYDRO-04
First Submitted: August 20, 2018
First Posted: August 22, 2018
Results First Submitted: October 8, 2018
Results First Posted: June 20, 2019
Last Update Posted: June 20, 2019