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

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ClinicalTrials.gov Identifier: NCT03415243
Recruitment Status : Completed
First Posted : January 30, 2018
Last Update Posted : May 22, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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

Condition or disease Intervention/treatment Phase
Common Cold Drug: Acetaminophen 650 mg + Dextromethorphan 20 mg + Phenylephrine 10 mg Drug: Acetaminophen 325 mg + Dextromethorphan 10 mg + Phenylephrine 5mg Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 1, 2018
Actual Primary Completion Date : March 29, 2018
Actual Study Completion Date : March 29, 2018


Arm Intervention/treatment
Experimental: Treatment A Group
Participants will receive a single dose (1 sachet) of the investigational product (Acetaminophen 650 mg + Dextromethorphan 20 mg + Phenylephrine 10 mg).
Drug: Acetaminophen 650 mg + Dextromethorphan 20 mg + Phenylephrine 10 mg
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, [µL]) of 99mTc-DTPA (Technetium-99m-diethylene-triamine-pentaacetate will be added to the drug solution in to achieve a maximum of 108 curie(µCi) 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.

Experimental: Treatment B Group
Participants will receive a single dose (2 caplets) of the investigational product (Acetaminophen 325 mg + Dextromethorphan 10 mg + Phenylephrine 5mg).
Drug: Acetaminophen 325 mg + Dextromethorphan 10 mg + Phenylephrine 5mg
Caplet doses will be prepared by drilling a hole of approximately 1 millimetre (mm) diameter and at a depth of approximately one-half of its thickness (~2-2.5 mm deep) into individual caplets. 99mTc-DTPA (dissolved in normal saline) will be added into the hole of each caplet as a low volume liquid (0.5-2.0 µL) to achieve a maximum of 54 µCi (2 MBq) per individual caplet at the time of dosing (two caplets = 108 µCi (4 MBq) dose per assessment visit). The applied liquid will be allowed to air dry and the hole will be filled with the equivalent powder blend from a crushed caplet such that the drug content will remain constant and same for all caplets. The caplet will be sealed with an appropriate material if determined to be necessary. Radiolabeled caplets will be packaged as unit doses (2 caplets per container) and maintained at room temperature until administration. Caplets will be swallowed with 225 mL of non-carbonated room temperature water within 30 seconds.




Primary Outcome Measures :
  1. Mean time to onset of gastric emptying [ Time Frame: up to 10 hours post drug administration of Day 1 ]
    Scintigraphic imaging will be performed immediately following ingestion of the radiolabeled drug formulation and data will be recorded and stored. Images will be analyzed in a time-lapse format. Regions of interest (ROI) will be drawn to include the stomach, proximal small intestine, distal small intestine and colon. Each image will be corrected for radioactive decay and background radiation. Mean time to onset of gastric emptying will be evaluated.

  2. Mean time to complete gastric emptying [ Time Frame: up to 10 hours post drug administration of Day 1 ]
    Scintigraphic imaging will be performed immediately following ingestion of the radiolabeled drug formulation and data will be recorded and stored. Images will be analyzed in a time-lapse format. ROI will be drawn to include the stomach, proximal small intestine, distal small intestine and colon. Each image will be corrected for radioactive decay and background radiation. Mean time to complete gastric emptying will be evaluated.

  3. Characterize gastrointestinal emptying by measuring GE25% values [ Time Frame: up to 10 hours post drug administration of Day 1 ]
    Scintigraphic imaging will be performed immediately following ingestion of the radiolabeled drug formulation and data will be recorded and stored. Images will be analyzed in a time-lapse format. ROI will be drawn to include the stomach, proximal small intestine, distal small intestine and colon Each image will be corrected for radioactive decay and background radiation. Time for tracer to leave the stomach i.e. GE25% values will be evaluated.

  4. Characterize gastrointestinal emptying by measuring GE50% values [ Time Frame: up to 10 hours post drug administration of Day 1 ]
    Scintigraphic imaging will be performed immediately following ingestion of the radiolabeled drug formulation and data will be recorded and store. Images will be analyzed in a time-lapse format. ROI will be drawn to include the stomach, proximal small intestine, distal small intestine and colon. Each image will be corrected for radioactive decay and background radiation. Time for tracer to leave the stomach i.e. GE50% will be evaluated.

  5. Characterize gastrointestinal emptying by measuring GE90% values [ Time Frame: up to 10 hours post drug administration of Day 1 ]
    Scintigraphic imaging will be performed immediately following ingestion of the radiolabeled drug formulation and data will be recorded and stored. Images will be analyzed in a time-lapse format. ROI will be drawn to include the stomach, proximal small intestine, distal small intestine and colon. Each image will be corrected for radioactive decay and background radiation. Time for tracer to leave the stomach i.e. GE90% values will be evaluated.

  6. Amount of drug remaining in the stomach after administration at different timepoints [ Time Frame: up to 10 hours post drug administration of Day 1 ]
    Scintigraphic imaging will be performed immediately following ingestion of the radiolabeled drug formulation and data will be recorded and stored. Images will be analyzed in a time-lapse format. ROI will be drawn to include the stomach, proximal small intestine, distal small intestine and colon. Each image will be corrected for radioactive decay and background radiation. Amount of drug (labelled with tracer) remaining in the stomach after administration at different timepoints i.e. at 15, 30, 45, 60, 75, 90, 105, 120, 180, 240 mins will be determined.

  7. Sectional areas under the gastric emptying curve and Total AUC [ Time Frame: up to 10 hours post drug administration of Day 1 ]
    Scintigraphic imaging will be performed immediately following ingestion of the radiolabeled drug formulation and data will be recorded and stored. Images will be analyzed in a time-lapse format. ROI will be drawn to include the stomach, proximal small intestine, distal small intestine and colon. Each image will be corrected for radioactive decay and background radiation. Sectional areas under the gastric emptying curve will be calculated using the data.

  8. Total Area under the curve (AUC) [ Time Frame: up to 10 hours post drug administration of Day 1 ]
    Scintigraphic imaging will be performed immediately following ingestion of the radiolabeled drug formulation and data will be recorded and stored. Images will be analyzed in a time-lapse format. ROI will be drawn to include the stomach, proximal small intestine, distal small intestine and colon. Each image will be corrected for radioactive decay and background radiation. Total Area under the curve will be calculated using the data.

  9. Gastric emptying t half (t-1/2) value [ Time Frame: up to 10 hours post drug administration of Day 1 ]
    Scintigraphic imaging will be performed immediately following ingestion of the radiolabeled drug formulation and data will be recorded and stored. Scintigraphic images will be analyzed in a time-lapse format. ROI will be drawn to include the stomach, proximal small intestine, distal small intestine and colon Each image will be corrected for radioactive decay and background radiation. T-1/2 value will be calculated.

  10. Small intestinal transit time [ Time Frame: up to 10 hours post drug administration of Day 1 ]
    Scintigraphic imaging will be performed immediately following ingestion of the radiolabeled drug formulation and data will be recorded and stored electronically. Images will be analyzed in a time-lapse format. ROI will be drawn to include the stomach, proximal small intestine, distal small intestine and colon. Each image will be corrected for radioactive decay and background radiation. Small intestinal transit time will be calculated by determining the arrival time of the radioactive marker at the cecum / colon region and subtracting the gastric emptying value.


Secondary Outcome Measures :
  1. Safety (Adverse events Monitoring) [ Time Frame: From Baseline, to 5 days following last administration of investigational product ]
    Adverse events (AEs) will be monitored and recorded.

  2. Safety (Laboratory Evaluations) [ Time Frame: At Baseline and Day 1 ]
    Blood and urine Human Biological Samples (HBS) will be collected for safety laboratory tests.



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Ages Eligible for Study:   21 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03415243


Locations
United States, Kentucky
GSK Investigational Site
Lexington, Kentucky, United States, 40504
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03415243     History of Changes
Other Study ID Numbers: 208821
First Posted: January 30, 2018    Key Record Dates
Last Update Posted: May 22, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Common Cold
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Acetaminophen
Phenylephrine
Oxymetazoline
Dextromethorphan
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Cardiotonic Agents
Mydriatics
Autonomic Agents
Sympathomimetics
Vasoconstrictor Agents
Nasal Decongestants
Respiratory System Agents
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents