- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01858831
Single Oral Dose Study of Atovaquone/Proguanil Hydrochloride Combination Tablets and Atovaquone Suspension
Single Oral Dose Study of Atovaquone/Proguanil Hydrochloride Combination Tablets and Atovaquone Suspension. - A Single Oral Dose Study to Investigate Pharmacokinetics of Atovaquone and Proguanil From Combination Tablets and Atovaquone From Atovaquone Suspension in Japanese Healthy Males. -
This study will be a single-center, phase I, randomized, open, in fed condition, parallel, single dose study to evaluate the pharmacokinetics and the safety, tolerability of Atovaquone/proguanil combination tablets and atovaquone suspension in Japanese healthy male subjects.
Serial blood samples will be collected for the determination of the plasma concentration of atovaquone, proguanil and cycloguanil after dosing of atovaquone 1000mg/proguanil 400 mg and the plasma atovaquone concentration of atovaquone 750 and 1500 mg. Safety assessments will be performed for each treatment group.
CYP2C19 contribute to proguanil metabolism. CYP2C19 genotype will be determined in atovaquone/proguanil dosing group.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Kagoshima, Japan, 890-0081
- GSK Investigational Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Healthy as defined as being free from clinically significant illness or disease as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital sign, laboratory tests and ECG.
- Japanese healthy male between 20 and 55 years of age inclusive, at the time of signing the informed consent.
- Body weight => 50 kg and BMI within the range 18.5- 25 kg/m2
- Non-smoker or ex-smoker having ceased smoking for at least 6 months. (inclusive).
- ALT, alkaline phosphatase and bilirubin below the upper limit of normal (ULN)
- Single QTcB< 450 msec.
- Vital sign within the following ranges; Systolic blood pressure: < 90 mmHg or > 140 mmHg, Diastolic blood pressure: < 45 mmHg or > 90 mmHg, Plus rate: < 45 bpm or > 100 bpm, Body temperature: 37.5 C
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion Criteria:
- A positive results of syphilis, HBs antigen, HCV antibody, HIV antibody and HTLV-1 antibody at the time of screening.
- History of any cardiac diseases irrespective of with or without symptom.
- An episode of cardiac syncope within one year before screening period.
- History/evidence of clinically significant pulmonary diseases and hyper/hypo-thyroidism.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug screen.
- History of regular alcohol consumption exceeding, on average, 14 drinks/week for men (1 drink = 5 ounces (150 mL) of wine or 350 mL of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits) within 6 months of screening.
- The subject had participated in a clinical study or post-marketing study with an investigational or a non-investigational product during the previous 4 months preceding the administration of study medication of this study.
- The subject had participated in a clinical study or post-marketing study with an investigational or a non-investigational product during the previous 4 months preceding the administration of study medication of this study.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Unable to refrain from the use of alcohol, prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy excluding pollen allergy without current symptoms.
- Where participation in the study would result in donation of blood or blood products in excess of 400 mL within a 4 month or 200 mL within 2 month.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Atovaquone/proguanil HCL
|
Atovaquone/proguanil HCL
|
Active Comparator: Atovaquone 750 mg
|
Atovaquone
|
Active Comparator: Atovaquone 1500 mg
|
Atovaquone
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
plasma atovaquone concentration
Time Frame: pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose
|
pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose
|
plasma proguanil concentration
Time Frame: pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose
|
pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose
|
plasma cycloguanil concentration
Time Frame: pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose
|
pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with adverse events
Time Frame: up to 336h post dose
|
up to 336h post dose
|
|
Change in Systolic Blood Pressure
Time Frame: at pre-dose, 4, 24, 72, 168 and 336 h post-dose
|
Change values at 4, 24, 72, 168 and 336 h post-dose from baseline (pre-dose)
|
at pre-dose, 4, 24, 72, 168 and 336 h post-dose
|
Change in ECG findings
Time Frame: at pre-dose, 4, 72, 168 and 336 h post-dose
|
Change at 4, 72, 168 and 336 h post-dose from baseline (pre-dose)
|
at pre-dose, 4, 72, 168 and 336 h post-dose
|
Laboratory
Time Frame: at pre-dose, 72, 168 and 336 h post-dose
|
Change values at 72, 168 and 336 h post-dose from baseline (pre-dose)
|
at pre-dose, 72, 168 and 336 h post-dose
|
Change in Diastolic Blood Pressure
Time Frame: at pre-dose, 4, 24, 72, 168 and 336 h post-dose
|
Change values at 4, 24, 72, 168 and 336 h post-dose from baseline (pre-dose)
|
at pre-dose, 4, 24, 72, 168 and 336 h post-dose
|
Change in Heart rate
Time Frame: at pre-dose, 4, 24, 72, 168 and 336 h post-dose
|
Change values at 4, 24, 72, 168 and 336 h post-dose from baseline (pre-dose)
|
at pre-dose, 4, 24, 72, 168 and 336 h post-dose
|
Change in Hematology values
Time Frame: at pre-dose, 72, 168 and 336 h post-dose
|
Change values at 72, 168 and 336 h post-dose from baseline (pre-dose)
|
at pre-dose, 72, 168 and 336 h post-dose
|
Change in Biochemistry values
Time Frame: at pre-dose, 72, 168 and 336 h post-dose
|
Change values at 72, 168 and 336 h post-dose from baseline (pre-dose)
|
at pre-dose, 72, 168 and 336 h post-dose
|
Change in Urinalysis values
Time Frame: at pre-dose, 72, 168 and 336 h post-dose
|
Change values at 72, 168 and 336 h post-dose from baseline (pre-dose)
|
at pre-dose, 72, 168 and 336 h post-dose
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 116441
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