Single Oral Dose Study of Atovaquone/Proguanil Hydrochloride Combination Tablets and Atovaquone Suspension

NCT ID: NCT01858831

Last Updated: 2017-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2012-05-31

Brief Summary

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.

Conditions

Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Atovaquone/proguanil HCL

Atovaquone/proguanil HCL

Group Type: EXPERIMENTAL

Atovaquone/proguanil HCL

Intervention Type: DRUG

Atovaquone/proguanil HCL

Atovaquone 750 mg

Atovaquone 750 mg

Group Type: ACTIVE_COMPARATOR

Atovaquone

Intervention Type: DRUG

Atovaquone

Atovaquone 1500 mg

Atovaquone 1500 mg

Group Type: ACTIVE_COMPARATOR

Atovaquone

Intervention Type: DRUG

Atovaquone

Interventions

Atovaquone/proguanil HCL

Atovaquone/proguanil HCL

Intervention Type: DRUG

Atovaquone

Atovaquone

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Kagoshima, , Japan

Countries

Japan

Other Identifiers

116441

Identifier Type: -

Identifier Source: org_study_id