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

March 21, 2017 updated by: GlaxoSmithKline

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

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Kagoshima, Japan, 890-0081
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 53 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

March 15, 2012

First Submitted That Met QC Criteria

May 16, 2013

First Posted (Estimate)

May 21, 2013

Study Record Updates

Last Update Posted (Actual)

March 22, 2017

Last Update Submitted That Met QC Criteria

March 21, 2017

Last Verified

March 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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