To Investigate the Gastrointestinal Behaviour of Two Triple Combination Products in Healthy Male Volunteers
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 Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 1
Contacts and Locations
Study Locations
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Kentucky
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Lexington, Kentucky, United States, 40504
- GSK Investigational Site
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Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
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Experimental: Treatment A Group
Participants will receive a single dose (1 sachet) of the investigational product (Acetaminophen 650mg+Dextromethorphan 20mg+Phenylephrine 10mg).
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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.
Other Names:
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Experimental: Treatment B Group
Participants will receive a single dose (2 caplets) of the investigational product (Acetaminophen 325mg+Dextromethorphan 10mg+Phenylephrine 5mg).
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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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Mean Time to Onset of Gastric Emptying
Time Frame: Predose until 10 hours post dose on Day 1
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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.
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Predose until 10 hours post dose on Day 1
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Mean Time to Complete Gastric Emptying
Time Frame: Predose until 10 hours post dose on Day 1
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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.
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Predose until 10 hours post dose on Day 1
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Mean Time for Gastric Emptying by Measuring 25 Percent Values
Time Frame: Predose until 10 hours post dose on Day 1
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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.
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Predose until 10 hours post dose on Day 1
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Mean Time for Gastric Emptying by Measuring 50 Percent Values
Time Frame: Predose until 10 hours post dose on Day 1
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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.
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Predose until 10 hours post dose on Day 1
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Mean Time for Gastric Emptying by Measuring 90 Percent Values
Time Frame: Predose until 10 hours post dose on Day 1
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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.
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Predose until 10 hours post dose on Day 1
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Percentage of Radiolabeled Drug Remaining in the Stomach After 15 Minutes of Administration
Time Frame: 15 minutes post dose on Day 1
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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.
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15 minutes post dose on Day 1
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Percentage of Radiolabeled Drug Remaining in the Stomach After 30 Minutes of Administration
Time Frame: 30 minutes post dose on Day 1
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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.
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30 minutes post dose on Day 1
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Percentage of Radiolabeled Drug Remaining in the Stomach After 45 Minutes of Administration
Time Frame: 45 minutes post dose on Day 1
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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.
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45 minutes post dose on Day 1
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Percentage of Radiolabeled Drug Remaining in the Stomach After 60 Minutes of Administration
Time Frame: 60 minutes post dose on Day 1
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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.
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60 minutes post dose on Day 1
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Percentage of Radiolabeled Drug Remaining in the Stomach After 75 Minutes of Administration
Time Frame: 75 minutes post dose on Day 1
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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.
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75 minutes post dose on Day 1
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Percentage of Radiolabeled Drug Remaining in the Stomach After 90 Minutes of Administration
Time Frame: 90 minutes post dose on Day 1
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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.
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90 minutes post dose on Day 1
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Percentage of Radiolabeled Drug Remaining in the Stomach After 105 Minutes of Administration
Time Frame: 105 minutes post dose on Day 1
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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.
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105 minutes post dose on Day 1
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Percentage of Radiolabeled Drug Remaining in the Stomach After 120 Minutes of Administration
Time Frame: 120 minutes post dose on Day 1
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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.
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120 minutes post dose on Day 1
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Percentage of Radiolabeled Drug Remaining in the Stomach After 180 Minutes of Administration
Time Frame: 180 minutes post dose on Day 1
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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.
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180 minutes post dose on Day 1
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Percentage of Radiolabeled Drug Remaining in the Stomach After 240 Minutes of Administration
Time Frame: 240 minutes post dose on Day 1
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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.
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240 minutes post dose on Day 1
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Area Under the Gastric Emptying Curve From Time 0 to 15 Minutes
Time Frame: 15 minutes post dose on Day 1
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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.
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15 minutes post dose on Day 1
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Area Under the Gastric Emptying Curve From Time 0 to 30 Minutes
Time Frame: 30 minutes post dose on Day 1
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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.
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30 minutes post dose on Day 1
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Area Under the Gastric Emptying Curve From Time 0 to 45 Minutes
Time Frame: 45 minutes post dose on Day 1
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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.
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45 minutes post dose on Day 1
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Area Under the Gastric Emptying Curve From Time 0 to 60 Minutes
Time Frame: 60 minutes post dose on Day 1
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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.
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60 minutes post dose on Day 1
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Area Under the Gastric Emptying Curve From Time 0 to 75 Minutes
Time Frame: 75 minutes post dose on Day 1
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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.
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75 minutes post dose on Day 1
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Area Under the Gastric Emptying Curve From Time 0 to 90 Minutes
Time Frame: 90 minutes post dose on Day 1
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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.
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90 minutes post dose on Day 1
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Area Under the Gastric Emptying Curve From Time 0 to 105 Minutes
Time Frame: 105 minutes post dose on Day 1
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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.
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105 minutes post dose on Day 1
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Area Under the Gastric Emptying Curve From Time 0 to 120 Minutes
Time Frame: 120 minutes post dose on Day 1
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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.
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120 minutes post dose on Day 1
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Area Under the Gastric Emptying Curve From Time 0 to 180 Minutes
Time Frame: 180 minutes post dose on Day 1
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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.
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180 minutes post dose on Day 1
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Area Under the Gastric Emptying Curve From Time 0 to 240 Minutes
Time Frame: 240 minutes post dose on Day 1
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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.
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240 minutes post dose on Day 1
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Total Area Under the Gastric Emptying Curve
Time Frame: Predose until 10 hours post dose on Day 1
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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.
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Predose until 10 hours post dose on Day 1
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Gastric Emptying Half-Life
Time Frame: Predose until 10 hours post dose on Day 1
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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.
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Predose until 10 hours post dose on Day 1
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Small Intestine Transit Time
Time Frame: Predose until 10 hours post dose on Day 1
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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.
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Predose until 10 hours post dose on Day 1
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Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Number of Participants With Clinically Significant Change in Laboratory Test Values
Time Frame: From baseline up to Day 1
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Haematological, biochemistry, urinalysis and virological parameters were analyzed.
Clinical significance was judged by the investigator based upon the out of range values of standard range set for each parameter.
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From baseline up to Day 1
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Collaborators and Investigators
Sponsor
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Picornaviridae Infections
- Common Cold
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Analgesics, Non-Narcotic
- Antipyretics
- Protective Agents
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Cardiotonic Agents
- Respiratory System Agents
- Antitussive Agents
- Sympathomimetics
- Vasoconstrictor Agents
- Mydriatics
- Nasal Decongestants
- Adrenergic alpha-1 Receptor Agonists
- Acetaminophen
- Dextromethorphan
- Phenylephrine
- Oxymetazoline
Other Study ID Numbers
Other Study ID Numbers
- 208821
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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