To Investigate the Gastrointestinal Behaviour of Two Triple Combination Products in Healthy Male Volunteers

NCT03415243 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 208821
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Common Cold

Outcome Measures

Primary Outcomes (28)

• Mean Time to Onset of Gastric Emptying

  Mean time to onset of gastric emptying in participants who did not vomit shortly (within 60 minutes) after study drug administration was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 microcurie \[mcCi\] isotope-technetium-99m-diethylene-triamine-pentaacetate \[DTPA\]). Data images were analyzed in a time-lapse format and corrected for radioactive decay and background radiation. Regions of interest (ROI) included the stomach, proximal small intestine, distal small intestine and colon.

  Predose until 10 hours post dose on Day 1

• Mean Time to Complete Gastric Emptying

  Mean time to complete gastric emptying in participants who did not vomit shortly (within 60 minutes) after study drug administration was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m-DTPA). Data images were analyzed in a time-lapse format and corrected for radioactive decay and background radiation. ROI included the stomach, proximal small intestine, distal small intestine and colon.

  Predose until 10 hours post dose on Day 1

• Mean Time for Gastric Emptying by Measuring 25 Percent Values

  Mean time to gastric emptying by 25 percent (GE25%) was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA). Data images were analyzed in a time-lapse format and corrected for radioactive decay and background radiation. ROI included the stomach, proximal small intestine, distal small intestine and colon.

  Predose until 10 hours post dose on Day 1

• Mean Time for Gastric Emptying by Measuring 50 Percent Values

  Mean time to gastric emptying by 50 percent (GE50%) was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA). Data images were analyzed in a time-lapse format and corrected for radioactive decay and background radiation. ROI included the stomach, proximal small intestine, distal small intestine and colon.

  Predose until 10 hours post dose on Day 1

• Mean Time for Gastric Emptying by Measuring 90 Percent Values

  Mean time to gastric emptying by 90 percent (GE90%) was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA). Data images were analyzed in a time-lapse format and corrected for radioactive decay and background radiation. ROI included the stomach, proximal small intestine, distal small intestine and colon.

  Predose until 10 hours post dose on Day 1

• Percentage of Radiolabeled Drug Remaining in the Stomach After 15 Minutes of Administration

  Percentage of radiolabeled drug remaining in the stomach was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 15 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  15 minutes post dose on Day 1

• Percentage of Radiolabeled Drug Remaining in the Stomach After 30 Minutes of Administration

  Percentage of radiolabeled drug remaining in the stomach was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 30 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  30 minutes post dose on Day 1

• Percentage of Radiolabeled Drug Remaining in the Stomach After 45 Minutes of Administration

  Percentage of radiolabeled drug remaining in the stomach was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 45 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  45 minutes post dose on Day 1

• Percentage of Radiolabeled Drug Remaining in the Stomach After 60 Minutes of Administration

  Percentage of radiolabeled drug remaining in the stomach was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 60 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  60 minutes post dose on Day 1

• Percentage of Radiolabeled Drug Remaining in the Stomach After 75 Minutes of Administration

  Percentage of radiolabeled drug remaining in the stomach was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 75 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  75 minutes post dose on Day 1

• Percentage of Radiolabeled Drug Remaining in the Stomach After 90 Minutes of Administration

  Percentage of radiolabeled drug remaining in the stomach was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 90 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  90 minutes post dose on Day 1

• Percentage of Radiolabeled Drug Remaining in the Stomach After 105 Minutes of Administration

  Percentage of radiolabeled drug remaining in the stomach was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 105 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  105 minutes post dose on Day 1

• Percentage of Radiolabeled Drug Remaining in the Stomach After 120 Minutes of Administration

  Percentage of radiolabeled drug remaining in the stomach was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 120 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  120 minutes post dose on Day 1

• Percentage of Radiolabeled Drug Remaining in the Stomach After 180 Minutes of Administration

  Percentage of radiolabeled drug remaining in the stomach was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 180 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  180 minutes post dose on Day 1

• Percentage of Radiolabeled Drug Remaining in the Stomach After 240 Minutes of Administration

  Percentage of radiolabeled drug remaining in the stomach was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 240 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  240 minutes post dose on Day 1

• Area Under the Gastric Emptying Curve From Time 0 to 15 Minutes

  Area under the gastric emptying curve from time 0 to 15 was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 15 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  15 minutes post dose on Day 1

• Area Under the Gastric Emptying Curve From Time 0 to 30 Minutes

  Area under the gastric emptying curve from time 0 to 30 was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 30 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  30 minutes post dose on Day 1

• Area Under the Gastric Emptying Curve From Time 0 to 45 Minutes

  Area under the gastric emptying curve from time 0 to 45 was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 45 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  45 minutes post dose on Day 1

• Area Under the Gastric Emptying Curve From Time 0 to 60 Minutes

  Area under the gastric emptying curve from time 0 to 60 was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 60 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  60 minutes post dose on Day 1

• Area Under the Gastric Emptying Curve From Time 0 to 75 Minutes

  Area under the gastric emptying curve from time 0 to 75 was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 75 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  75 minutes post dose on Day 1

• Area Under the Gastric Emptying Curve From Time 0 to 90 Minutes

  Area under the gastric emptying curve from time 0 to 90 was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 90 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  90 minutes post dose on Day 1

• Area Under the Gastric Emptying Curve From Time 0 to 105 Minutes

  Area under the gastric emptying curve from time 0 to 105 was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 105 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  105 minutes post dose on Day 1

• Area Under the Gastric Emptying Curve From Time 0 to 120 Minutes

  Area under the gastric emptying curve from time 0 to 120 was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 120 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  120 minutes post dose on Day 1

• Area Under the Gastric Emptying Curve From Time 0 to 180 Minutes

  Area under the gastric emptying curve from time 0 to 180 was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 180 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  180 minutes post dose on Day 1

• Area Under the Gastric Emptying Curve From Time 0 to 240 Minutes

  Area under the gastric emptying curve from time 0 to 240 was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA) and after 240 minutes of drug ingestion. Data images were analyzed and corrected for radioactive decay and background radiation.

  240 minutes post dose on Day 1

• Total Area Under the Gastric Emptying Curve

  Total area under the gastric emptying curve was evaluated by scintigraphic imaging, performed after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA). Data images were analyzed in a time-lapse format and corrected for radioactive decay and background radiation.

  Predose until 10 hours post dose on Day 1

• Gastric Emptying Half-Life

  Gastric emptying half-life was defined as the time required by the stomach to empty 50% of the ingested meal and was evaluated by scintigraphic imaging, performed immediately after ingestion of the investigational drug formulation (radiolabeled with not more than 108 mcCi isotope-technetium-99m DTPA). Data images were analyzed in a time-lapse format and corrected for radioactive decay and background radiation.

  Predose until 10 hours post dose on Day 1

• Small Intestine Transit Time

  Small intestinal transit time was calculated by determining the arrival time of the radiolabeled investigational drug formulation at the cecum or colon region from scintigraphic imaging and subtracting the gastric emptying value.

  Predose until 10 hours post dose on Day 1

Secondary Outcomes (1)

• Number of Participants With Clinically Significant Change in Laboratory Test Values

  From baseline up to Day 1

Study Arms (2)

Treatment A Group

EXPERIMENTAL

Participants will receive a single dose (1 sachet) of the investigational product (Acetaminophen 650mg+Dextromethorphan 20mg+Phenylephrine 10mg).

Drug: Acetaminophen 650mg+Dextromethorphan 20mg+Phenylephrine 10mg

Treatment B Group

EXPERIMENTAL

Participants will receive a single dose (2 caplets) of the investigational product (Acetaminophen 325mg+Dextromethorphan 10mg+Phenylephrine 5mg).

Drug: Acetaminophen 325mg+Dextromethorphan 10mg+Phenylephrine 5mg

Interventions

Acetaminophen 650mg+Dextromethorphan 20mg+Phenylephrine 10mg DRUG

Contents of the sachet will be emptied into a glass bottle and 225 mL of hot, but not boiling water (approximately 90-95°C), will be added to the container and mixed to dissolve the contents of the sachet. The dissolved solution will be allowed to cool to approximately 40 - 50 degree Celsius (°C). After cooling, a small volume (1 to 10 microliters \[mcL\]) of 99mTc-DTPA (Technetium-99m-diethylene-triamine-pentaacetate will be added to the drug solution in to achieve a maximum of 108 curie(mcCi) i.e.4 megabecquerel \[MBq\] per individual dose at the time of dosing. The container will be capped and maintained at a temperature between 35-45°C at time of dosing and then participants will be instructed to consume the hot drink entirely within 30 seconds.

Also known as: Theraflu daytime severe cold and cough powder

Treatment A Group

Acetaminophen 325mg+Dextromethorphan 10mg+Phenylephrine 5mg DRUG

Caplet doses will be prepared by drilling hole of approximately(app.)1millimetre(mm)diameter and app.2-2.5mm deep into individual caplets.99mTc-DTPA(dissolved in normal saline)will be added into hole of each caplet as low volume liquid(0.5-2.0mcL)to achieve maximum of 54 mcCi(2MBq)per caplet at time of dosing(2caplets=108 mcCi\[4MBq\]dose per assessment visit).Applied liquid will be allowed to air dry,hole to be filled with equivalent powder blend from crushed caplet so drug content will remain constant for all caplets.Caplet will be sealed with appropriate material.Radiolabeled caplets will be packaged as unit doses(2 caplets per container)and maintained at room temperature until administration.Caplets will be swallowed with 225mL of noncarbonated room temperature water within 30 seconds.

Also known as: Theraflu expressmax daytime severe cold and cough caplets

Treatment B Group

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Lexington, Kentucky, 40504, United States

Location

Related Publications (1)

• 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.

  PMID: 35135601 DERIVED

MeSH Terms

Conditions

Common Cold

Interventions

Acetaminophen; Dextromethorphan; Phenylephrine

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; 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; Ethanolamines; Amino Alcohols; Alcohols

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

• GSK Clinical Trials

  GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: January 30, 2018
• Study Start: March 1, 2018
• Primary Completion: March 29, 2018
• Study Completion: March 29, 2018
• Last Updated: June 24, 2019
• Results First Posted: June 24, 2019

Record last verified: 2019-03

Locations

US (1)