MalariaPhase 1NCT01858831
Single Oral Dose Study of Atovaquone/Proguanil Hydrochloride Combination Tablets and Atovaquone Suspension
A Phase 1 study testing Atovaquone/proguanil HCL and Atovaquone in people with Malaria, run by GlaxoSmithKline at 1 site in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- Atovaquone/proguanil HCL and Atovaquone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteJapan
- Study dates
- Apr 2012to May 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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 locations and contacts
1 site in 1 country.
About this study
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. -
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
- Being tested
- Atovaquone/proguanil HCL, Atovaquone
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atovaquone/proguanil HCLDrug
Atovaquone/proguanil HCL
AtovaquoneDrug
Atovaquone
| Study group | Role | What they receive |
|---|---|---|
| Atovaquone/proguanil HCL | Experimental | Atovaquone/proguanil HCL Receives: Drug: Atovaquone/proguanil HCL |
| Atovaquone 750 mg | Active comparator | Atovaquone 750 mg Receives: Drug: Atovaquone |
| Atovaquone 1500 mg | Active comparator | Atovaquone 1500 mg Receives: Drug: Atovaquone |
What is being measured
The primary outcome is the main question the study is designed to answer.
plasma atovaquone concentration
Measured: pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose
plasma proguanil concentration
Measured: pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose
plasma cycloguanil concentration
Measured: 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
Measured: up to 336h post dose
Change in Systolic Blood Pressure
Change values at 4, 24, 72, 168 and 336 h post-dose from baseline (pre-dose)
Measured: at pre-dose, 4, 24, 72, 168 and 336 h post-dose
Change in ECG findings
Change at 4, 72, 168 and 336 h post-dose from baseline (pre-dose)
Measured: at pre-dose, 4, 72, 168 and 336 h post-dose
Laboratory
Change values at 72, 168 and 336 h post-dose from baseline (pre-dose)
Measured: at pre-dose, 72, 168 and 336 h post-dose
Change in Diastolic Blood Pressure
Change values at 4, 24, 72, 168 and 336 h post-dose from baseline (pre-dose)
Measured: at pre-dose, 4, 24, 72, 168 and 336 h post-dose
Change in Heart rate
Change values at 4, 24, 72, 168 and 336 h post-dose from baseline (pre-dose)
Measured: at pre-dose, 4, 24, 72, 168 and 336 h post-dose
Change in Hematology values
Change values at 72, 168 and 336 h post-dose from baseline (pre-dose)
Measured: at pre-dose, 72, 168 and 336 h post-dose
Change in Biochemistry values
Change values at 72, 168 and 336 h post-dose from baseline (pre-dose)
Measured: at pre-dose, 72, 168 and 336 h post-dose
Change in Urinalysis values
Change values at 72, 168 and 336 h post-dose from baseline (pre-dose)
Measured: at pre-dose, 72, 168 and 336 h post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2013 (estimated)
- Study startApr 2012
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01858831
- Sponsor's protocol ID
- 116441
- Status last verified
- Mar 2017
- First submitted
- 15 Mar 2012
- Last updated
- 22 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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. -
- ClinicalTrials.gov ID
- NCT01858831
- Acronym / sponsor ID
- 116441
- Conditions
- Malaria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Apr 2012
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 21 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Atovaquone/proguanil HCL | Experimental | Drug: Atovaquone/proguanil HCLAtovaquone/proguanil HCL |
| Atovaquone 750 mg | Active comparator | Drug: AtovaquoneAtovaquone 750 mg |
| Atovaquone 1500 mg | Active comparator | Drug: AtovaquoneAtovaquone 1500 mg |
Who may qualify
- Ages
- 20 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (15 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atovaquone/proguanil HCLAtovaquone/proguanil HCL | Drug | Atovaquone/proguanil HCL |
| AtovaquoneAtovaquone | Drug | Atovaquone 1500 mg, Atovaquone 750 mg |
Primary outcome
plasma atovaquone concentration
Time frame: 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
plasma cycloguanil concentration
Time frame: pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose
9 secondary outcomes
Number of participants with adverse events
Time frame: 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 in ECG findings
Time frame: 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 in Diastolic Blood Pressure
Time frame: 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 in Hematology values
Time frame: 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 in Urinalysis values
Time frame: at pre-dose, 72, 168 and 336 h post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2017.
- Results for study 116441 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Atovaquone/proguanil HCL and Atovaquone in people with Malaria, run by GlaxoSmithKline at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
plasma atovaquone concentration (time frame: pre, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 120, 168, 216, 336 post dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2017.