Last updated: 11/07/2018 10:27:58
Single Oral Dose Study of Atovaquone/Proguanil Hydrochloride Combination Tablets and Atovaquone Suspension
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: 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. -
Trial description: 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.
Primary purpose:
Other
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
plasma atovaquone concentration
Timeframe: pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose
plasma proguanil concentration
Timeframe: pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose
plasma cycloguanil concentration
Timeframe: pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose
Secondary outcomes:
Number of participants with adverse events
Timeframe: up to 336h post dose
Change in Systolic Blood Pressure
Timeframe: at pre-dose, 4, 24, 72, 168 and 336 h post-dose
Change in ECG findings
Timeframe: at pre-dose, 4, 72, 168 and 336 h post-dose
Laboratory
Timeframe: at pre-dose, 72, 168 and 336 h post-dose
Change in Diastolic Blood Pressure
Timeframe: at pre-dose, 4, 24, 72, 168 and 336 h post-dose
Change in Heart rate
Timeframe: at pre-dose, 4, 24, 72, 168 and 336 h post-dose
Change in Hematology values
Timeframe: at pre-dose, 72, 168 and 336 h post-dose
Change in Biochemistry values
Timeframe: at pre-dose, 72, 168 and 336 h post-dose
Change in Urinalysis values
Timeframe: at pre-dose, 72, 168 and 336 h post-dose
Interventions:
Enrollment:
30
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Hiroko Ino, Naoki Takahashi, Hirofumi Hashimoto, Yohei Doi, Toshiyasu Hirama. Phase 1 study of atovaquine and atovaquone/proguanil HCl. J Infect Chemother. 2013;61(4):335-342.
Medical condition
Malaria
Product
atovaquone, atovaquone/proguanil, proguanil
Collaborators
Not applicable
Study date(s)
April 2012 to May 2012
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
20 - 55 years
Accepts healthy volunteers
Yes
- 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.
- 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.
Inclusion and exclusion criteria
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.
Trial location(s)
Study documents
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2012-23-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 116441 can be found on the GSK Clinical Study Register.
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