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

NCT01858831 | Completed Phase 1

• 1 other identifier: 116441
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (3)

• plasma atovaquone concentration

  pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose

• plasma proguanil concentration

  pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose

• plasma cycloguanil concentration

  pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose

Secondary Outcomes (9)

• Number of participants with adverse events

  up to 336h post dose

• Change in Systolic Blood Pressure

  at pre-dose, 4, 24, 72, 168 and 336 h post-dose

• Change in ECG findings

  at pre-dose, 4, 72, 168 and 336 h post-dose

• Laboratory

  at pre-dose, 72, 168 and 336 h post-dose

• Change in Diastolic Blood Pressure

  at pre-dose, 4, 24, 72, 168 and 336 h post-dose

Study Arms (3)

Atovaquone/proguanil HCL

EXPERIMENTAL

Atovaquone/proguanil HCL

Drug: Atovaquone/proguanil HCL

Atovaquone 750 mg

ACTIVE COMPARATOR

Atovaquone 750 mg

Drug: Atovaquone

Atovaquone 1500 mg

ACTIVE COMPARATOR

Atovaquone 1500 mg

Drug: Atovaquone

Interventions

Atovaquone/proguanil HCL DRUG

Atovaquone/proguanil HCL

Atovaquone/proguanil HCL

Atovaquone DRUG

Atovaquone

Atovaquone 1500 mg; Atovaquone 750 mg

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Kagoshima, 890-0081, Japan

Location

Related Links

• Results for study 116441 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Malaria

Interventions

Atovaquone; Proguanil

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Naphthoquinones; Quinones; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Biguanides; Guanidines; Amidines

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2012
• First Posted: May 21, 2013
• Study Start: April 1, 2012
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: March 22, 2017

Record last verified: 2017-03

Locations

JP (1)