Clinical trial NCT03415243: To Investigate the Gastrointestinal Behaviour of Two Triple Combination Products in Healthy Male Volunteers
Official title: A Single Dose, Open Label, Randomized Scintigraphic Study to Investigate the Gastrointestinal Behavior of 2 Triple Combination Products (Acetaminophen, Phenylephrine and Dextromethorphan) in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Common Cold
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2018-01-30
Enrollment: 28
Sex: MALE
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This clinical study will be conducted to characterize the gastrointestinal transit of two multi-symptoms formulations by inclusion of a radiolabel marker.

Detailed description: This study will be an open label, randomized, single dose, parallel groups gamma scintigraphic study. A total of 28 healthy male participants will be randomized (14 participantper treatment arm) in order to have 24 evaluable participants (12 participants per treatment arm). Participants will be randomized to receive either a single dose Treatment A (Theraflu daytime Severe Cold \& Cough powder) or single dose of Treatment B (Theraflu ExpressMax Daytime Severe Cold and Cough caplets). This study will consist of screening visit (Visit 1), followed by a treatment visit (Visit 2). Visit 2 includes two days: Day -1 and Day 1. On visit 2 (day -1) of the study, the study participants will be admitted to the unit at approximately 7 pm on the evening before study drug administration and will receive a standardized meal. Participants will be required to fast (nothing to eat or drink except non-carbonated water) from 10 hours prior until 4 hours after study drug administration. Water will be permitted until 1 hour prior to investigational product administration, and no additional fluids until the lunch meal will be served at approximately 4 hours post dose. Participants will then be given a standard lunch at 4 hours post-dose, a standard dinner at 10 hours post-dose on Day 1. Participants will be discharged from the unit after the last scintigraphic imaging is performed, blood sample for laboratory test will be taken as well as a brief physical examination. Scintigraphic acquisitions will be taken beginning after dose administration until 10 hours post-dose.

Eligibility criteria: Inclusion Criteria:

* Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study before any assessment is performed.
* Healthy male participants who, at the time of screening, are between the ages of 21 and 45 years, inclusive.
* Participants who are willing and able to comply with scheduled visits, treatment plan, bio-imaging procedure, laboratory tests and other study procedures.
* Healthy participant which is defined as in general good physical health, as judged by the investigator and no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead Electrocardiogram (ECG) or clinical laboratory tests.
* Body Mass Index (BMI) of 17.5 to 30.5 kilogram per meter square (kg/m2); and a total body weight \>50 kg (110 lbs)

Exclusion Criteria:

* Participants who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or participants who are GSK employees directly involved in the conduct of the study.
* Participation in other studies involving investigational drug(s) within 30 days prior to study entry and/or during study participation.
* Acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
* Known or suspected intolerance or hypersensitivity or contraindication to the study materials (or closely related compounds) or any of their stated ingredients.
* Participant with known allergy or intolerance to any of the contents of the standard meals.
* Participant is vegetarian.
* Unwilling or unable to comply with the Lifestyle guidelines described in this protocol.
* Use of prescription or non-prescription drugs and dietary supplements within 14 days or 5 half-lives, whichever is longer, prior to the first dose of investigational product that are deemed by the investigator to have a potential impact on the study objectives results.
* Evidence or history of clinically significant laboratory abnormality, hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease within the last 5 years that may increase the risk associated with study participation.
* A positive urine drug screen, breath alcohol test or urine cotinine test during Screening or on Day -1 of the study.
* Any condition possibly affecting drug absorption (e.g., gastrectomy)
* A history of current or relevant previous non-self-limiting gastrointestinal disorders peptic ulcer disease and/or gastrointestinal bleeding.
* Currently suffering from disease known to impact gastric emptying, e.g. migraine, insulin-dependent diabetes mellitus.
* The participant has had radiation exposure from clinical trials, including from the present study, and from therapeutic or diagnostic exposure, but excluding background radiation, exceeding a target organ (colon) dose of 50 mSv (5 rems) from a single dose within the last 30 days or a cumulative dose of 150 mSv (15 rems) in the last 12 months. No participant whose occupation requires monitoring for radiation exposure will be enrolled in the study.
* Participants who have been exposed to ionising radiation in excess of 10 mSv (whole body effective dose) above background over the previous 3 years period as a result of occupational exposure or previous participation in research studies. Clinically justified (therapeutic or diagnostic) exposures are not included in this calculation.
* Renal disease or impaired renal function at screening as indicated by abnormal levels of serum creatinine or urea or the presence of clinically significant abnormal urinary constituents (e.g. albuminuria). Minor deviations of laboratory values from the normal range are permitted, if judged by the investigator to have no clinical relevance.
* History or current evidence of ongoing hepatic disease or impaired hepatic function at screening. A candidate will be excluded if more than one of the following lab value deviations are found: 1) AST/SGOT (≥ 1.2 ULN), ALT/SGPT (≥ 1.2 ULN), 2) GGT (≥ 1.2 ULN), ALP (≥ 1.2 ULN), 3) total bilirubin (≥ 1.2 mg/dL) Minor deviations of laboratory values from the normal range are permitted, if judged by the investigator to have no clinical relevance. Positive results in any of the virology tests for HIV-Ab, HCV-Ab, HBsAg and HBc-Ab (Total).
* Diagnosis of long QT syndrome or QTc \> 450 msec for males at screening.
* Participants who were intending to father a child in the 3 months following the study.
* Participants who were unwilling to follow contraception requirements
* Participant had any non-removable metal objects such as metal plates, screws etc. in their chest or abdominal area.
* History of regular alcohol consumption exceeding 14 drinks/week (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of Screening.
* Smokers defined as the use of tobacco products (including but not limited to: electronic-cigarettes, nicotine gums, nicotine lozenges, etc) during the 6 months prior to screening or a positive urine cotinine test at screening.
* Participant has consumed (eat or drink) grapefruit or grapefruit-related citrus fruits (e.g., Seville oranges, pomelos, pawpaw, dragon fruit, kiwi fruit, mango, passion fruit, pomegranate, rambutan, star fruit or products that contain these fruits) 14 days prior to the first dose of investigational product.
* Participants who have previously been enrolled in this study.

Primary outcomes:
measure: Mean Time to Onset of Gastric Emptying
timeFrame: Predose until 10 hours post dose on Day 1
measure: Mean Time to Complete Gastric Emptying
timeFrame: Predose until 10 hours post dose on Day 1
measure: Mean Time for Gastric Emptying by Measuring 25 Percent Values
timeFrame: Predose until 10 hours post dose on Day 1
measure: Mean Time for Gastric Emptying by Measuring 50 Percent Values
timeFrame: Predose until 10 hours post dose on Day 1
measure: Mean Time for Gastric Emptying by Measuring 90 Percent Values
timeFrame: Predose until 10 hours post dose on Day 1
measure: Percentage of Radiolabeled Drug Remaining in the Stomach After 15 Minutes of Administration
timeFrame: 15 minutes post dose on Day 1
measure: Percentage of Radiolabeled Drug Remaining in the Stomach After 30 Minutes of Administration
timeFrame: 30 minutes post dose on Day 1
measure: Percentage of Radiolabeled Drug Remaining in the Stomach After 45 Minutes of Administration
timeFrame: 45 minutes post dose on Day 1
measure: Percentage of Radiolabeled Drug Remaining in the Stomach After 60 Minutes of Administration
timeFrame: 60 minutes post dose on Day 1
measure: Percentage of Radiolabeled Drug Remaining in the Stomach After 75 Minutes of Administration
timeFrame: 75 minutes post dose on Day 1
measure: Percentage of Radiolabeled Drug Remaining in the Stomach After 90 Minutes of Administration
timeFrame: 90 minutes post dose on Day 1
measure: Percentage of Radiolabeled Drug Remaining in the Stomach After 105 Minutes of Administration
timeFrame: 105 minutes post dose on Day 1
measure: Percentage of Radiolabeled Drug Remaining in the Stomach After 120 Minutes of Administration
timeFrame: 120 minutes post dose on Day 1
measure: Percentage of Radiolabeled Drug Remaining in the Stomach After 180 Minutes of Administration
timeFrame: 180 minutes post dose on Day 1
measure: Percentage of Radiolabeled Drug Remaining in the Stomach After 240 Minutes of Administration
timeFrame: 240 minutes post dose on Day 1
measure: Area Under the Gastric Emptying Curve From Time 0 to 15 Minutes
timeFrame: 15 minutes post dose on Day 1
measure: Area Under the Gastric Emptying Curve From Time 0 to 30 Minutes
timeFrame: 30 minutes post dose on Day 1
measure: Area Under the Gastric Emptying Curve From Time 0 to 45 Minutes
timeFrame: 45 minutes post dose on Day 1
measure: Area Under the Gastric Emptying Curve From Time 0 to 60 Minutes
timeFrame: 60 minutes post dose on Day 1
measure: Area Under the Gastric Emptying Curve From Time 0 to 75 Minutes
timeFrame: 75 minutes post dose on Day 1
measure: Area Under the Gastric Emptying Curve From Time 0 to 90 Minutes
timeFrame: 90 minutes post dose on Day 1
measure: Area Under the Gastric Emptying Curve From Time 0 to 105 Minutes
timeFrame: 105 minutes post dose on Day 1
measure: Area Under the Gastric Emptying Curve From Time 0 to 120 Minutes
timeFrame: 120 minutes post dose on Day 1
measure: Area Under the Gastric Emptying Curve From Time 0 to 180 Minutes
timeFrame: 180 minutes post dose on Day 1
measure: Area Under the Gastric Emptying Curve From Time 0 to 240 Minutes
timeFrame: 240 minutes post dose on Day 1
measure: Total Area Under the Gastric Emptying Curve
timeFrame: Predose until 10 hours post dose on Day 1
measure: Gastric Emptying Half-Life
timeFrame: Predose until 10 hours post dose on Day 1
measure: Small Intestine Transit Time
timeFrame: Predose until 10 hours post dose on Day 1
Secondary outcomes:
measure: Number of Participants With Clinically Significant Change in Laboratory Test Values
timeFrame: From baseline up to Day 1
Other outcomes:
Locations:
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
affiliation: GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Mallefet P, Armogida M, Doll WJ, Page RC, Sandefer EP. A single-dose, open-label, randomized, scintigraphic study to investigate the gastrointestinal behavior of 2 triple-combination cold products (acetaminophen, phenylephrine, and dextromethorphan) in healthy male volunteers. Trials. 2022 Feb 8;23(1):128. doi: 10.1186/s13063-022-06037-x.