MalariaPhase 1NCT04002687

Determine the Tolerability and Safety of Atovaquone-proguanil (ATV-PG) Co-administered With Amodiaquine (AQ)

A Phase 1 study testing ATV-PG 1000-400 mg + AQ 612 mg in people with Malaria, run by Medicines for Malaria Venture at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Malaria
What is being tested?: ATV-PG 1000-400 mg + AQ 612 mg
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 44 participants
Where: 1 siteUnited Kingdom
Study dates: 4 Apr 2019to 29 Oct 2019
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 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

1) Male or female, of sub-Saharan African origin (both parents born in sub-Saharan Africa), aged ≥18 to ≤45 years at the date of signing informed consent which is defined as the beginning of the Screening Period.
2. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to follow the following contraception requirements. Contraception must start one complete menstrual cycle prior to the first day of dosing and continue until at least 90 days after the end of the systemic exposure of the study drug (90 days after the last study drug administration).
Female subjects who are documented as being of non-childbearing potential are exempt from contraception requirements. Documentation of non-childbearing potential must include at least one of the following criteria:
Postmenopausal - evidence of menopause based on a combination of amenorrhea for at least one year and increased serum follicle-stimulating hormone (FSH) level (> 30 IU/L), or
Surgical sterilization - evidence of hysterectomy and/or bilateral oophorectomy.
All female subjects of childbearing potential and all male subjects with female partnersof childbearing potential, who are pregnant or breastfeeding must practice highly effective or acceptable methods of contraception (defined below) when having heterosexual intercourse.

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Sexual abstinence, defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug treatment can be considered a highly effective method of contraception for female and male subjects. Reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the subject.
Contraception methods for female subjects in this study:
Hormonal contraception:
Combined i.e. oestrogen- and progestogen-containing (oral, intravaginal or transdermal)
Progestogen-only (oral, injectable or implantable)
Intrauterine hormone-releasing system (IUS)
Intrauterine device (IUD) or
Bilateral tubal occlusion
Male partner vasectomised (with documented evidence of azoospermia if possible)
(Male partner uses) male condom with or without spermicide
Cap, diaphragm, or sponge with spermicide
Contraception methods for male subjects in this study:
Male condom with or without spermicide
Vasectomy (with documented evidence of azoospermia if possible) 3. Subjects must agree not to donate sperm or ova from the time of the first administration of study medication until 3 months after the end of the systemic exposure of the study drugs. 4. Subjects must have a body weight of at least 50 kg and a body mass index (BMI) between 18-25.0 kg/m² inclusive at screening.
5. Satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluation (haematology, biochemistry, coagulation, and urinalysis) that is reasonably likely to interfere with the subject's participation in or ability to complete the study as assessed by the Investigator.
6. Ability to swallow 8 capsules/tablets at a time or consecutively. 7. Ability to provide written, personally signed, and dated informed consent to participate in the study, in accordance with the ICH Good Clinical Practice (GCP) Guideline E6 (R2) (2016) and applicable regulations, before completing any study-related procedures.
8. An understanding, ability, and willingness to fully comply with study procedures and restrictions.

Who cannot join

Current or recurrent disease (e.g., cardiovascular, haematological, neurological,endocrine, immunological, renal, hepatic or gastrointestinal or other conditions) that could affect the action, absorption, or disposition of ATV-PG or AQ, or could affect clinical assessments or clinical laboratory evaluations.
Any significant history of seizures or epilepsy.
Current or relevant history of physical or psychiatric illness that may require treatment or make the subject unlikely to fully comply with the requirements or complete the study, or any condition that presents undue risk from the investigational product or study procedures.
Any other significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study may influence the result of the study, or the subject's ability to participate in the study.
Documented retinopathy.
History of photosensitivity.

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History of malaria.
Subjects have travelled to malaria endemic regions for more than a total of 4 weeks within the past 12 months (as per Global Malaria Risk: https://www.malariasite.com/malaria-risk/ [20]-)
The history or presence of any of the following cardiac conditions: known structural cardiac abnormalities; family history of long QT syndrome; cardiac syncope or recurrent, idiopathic syncope; exercise related clinically significant cardiac events.
Any clinically significant abnormalities in rhythm, conduction or morphology of resting ECG or clinically important abnormalities that may interfere with the interpretation of QTc interval changes. This includes subjects with any of the following (at screening or Day -1):
Sinus node dysfunction.
Clinically significant PR (PQ) interval prolongation.
Intermittent second or third degree AV block.
Complete bundle branch block.
Sustained cardiac arrhythmia's including (but not limited to) atrial fibrillation or supraventricular tachycardia; any symptomatic arrhythmia with the exception of isolated extra systoles.
Abnormal T wave morphology which may impact on the QT/QTc assessment.
QT interval corrected using the Fridericia's formula (QTcF) > 450 ms (males and females).
Any other ECG abnormalities in the standard 12-lead ECG and 24-hour 12 lead Holter ECG or an equivalent assessment which in the opinion of the Investigator will interfere with the ECG analysis.
Subjects with borderline abnormalities may be included if the deviations do not pose a safety risk, and if agreed between the appointed Cardiologist and the PI.
Has vital signs outside of the following normal range at screening or Day -1:
Blood pressure (BP):
Supine BP (after at least 5 minutes of supine rest):
Systolic blood pressure: 90 - 140 mmHg.
Systolic blood pressure drop of >20mmHg on standing (at screening only)
Diastolic blood pressure: 40 - 90 mmHg. b. Pulse rate (after at least 5 minutes of supine rest):
Less than 40 or greater than 100 beats per minute 12. Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening; 13.
AST, ALT or bilirubin measurement above the laboratory reference ranges, at screening or Day -1.
Haemoglobin or platelet count outside of the laboratory reference ranges.
or any other clinically significant abnormal haematological measurement (per the Investigator's discretion). 14. Positive test results for alcohol or drugs of abuse at screening or Day -1. 15. Female subjects who are pregnant (including a positive serum pregnancy test at screening and on Day-1) or breastfeeding.
16. History or clinical evidence of substance and/or alcohol abuse within the 2 years before screening. Alcohol abuse is defined as regular weekly intake of more than 14 units (for both males and females), using the following NHS alcohol tracker http://www.nhs.uk/Tools/Pages/drinks-tracker.aspx. 17. Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products in any form (e.g., gum, patch, electronic cigarettes) within 3 months prior to the planned first day of dosing.
18. Has used any other prescription medication (excluding hormonal contraception, hormone replacement therapy) within 14 days or 10 half-lives (whichever is longer) prior to Day 1 of the dosing period that the Investigator judges is likely to interfere with the study or pose an additional risk in participating.
19. Has used any over-the-counter medication (including multivitamin, herbal, or homeopathic preparations; excluding paracetamol - up to 1g paracetamol per day permitted) during the 7 days or 5 half-lives of the drug (whichever is longer) prior to Day 1 of the dosing period, that the Investigator judges is likely to interfere with the study or pose an additional risk in participating.
20. Has used any medication listed on the Flockhart table (http://medicine.iupui.edu/clinpharm/ddis/main-table/) that is either a moderate or strong inhibitor or inducer of CYP450 within 30 days or 5 half-lives (whichever is longer) prior to the planned first day of dosing.
21. Has received an investigational product or been treated with an investigational device within 90 days or 5 half-lives (whichever is the longer) prior to first drug administration.
22. Known or suspected intolerance or hypersensitivity to the investigational product, atovaquone, proguanil or amodiaquine, any closely related compound, or any of the stated ingredients.
23. History of significant allergic reaction (anaphylaxis, angioedema) to any product (food, pharmaceutical, etc).
24. Has donated or lost 400 mL blood (excluding plasma) or more within the last 16 weeks preceding the first day of dosing.
25. Has a mental incapacity or language barriers precluding adequate understanding, cooperation, and compliance with the study requirements 26. An inability to follow a standardised diet and meal schedule or inability to fast, as required during the study.
27. Subjects have veins unsuitable for intravenous puncture or cannulation on either arm (e.g. veins that are difficult to locate access or puncture veins with a tendency to rupture during or after puncture).
28. Prior screen failure (where the cause of the screen failure is not deemed to be temporary), randomisation, participation, or enrolment in this study. Subjects who initially failed due to temporary non-medically significant issues are eligible for rescreening once the cause has resolved.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Richmond Pharmacology Ltd.
Croydon, London, CR7 7YE

Other trials in United Kingdom

About this study

Official title: A Randomized, Double-blind, Placebo Controlled Parallel Group Study in Heathy Adult Subjects to Determine the Tolerability and Safety of Atovaquone-proguanil (ATV-PG) Co-administered With Amodiaquine (AQ)

The aim of the study is to determine the tolerability and safety of ATV-PG + AQ, ATV-PG + AQ placebo, ATV-PG placebo + AQ, and ATV-PG placebo + AQ placebo administered once daily for 3 days to healthy adult male and female subjects.This study in healthy adults is the first step towards establishing the tolerability and safety of the approved doses of ATV-PG and AQ when co-administered. If considered acceptable based on the findings of this study, the tolerability, safety and PE will subsequently be assessed, within the target geographical areas.

Read the detailed description

Although the tolerability and safety of ATV-PG and AQ alone are well established, additive tolerability signals are possible on co-administration. Four treatment arms will be used: ATV-PG + AQ placebo, ATV-PG placebo + AQ, ATV-PG placebo + AQ placebo, as well as ATV-PG + AQ. This will facilitate discrimination of the contribution of the treatments to any tolerability signal. In the event that ATV-PG + AQ is not considered sufficiently well tolerated, data on the individual agents will provide an indication of whether ATV-PG or AQ are suitable partner drugs for other combinations.

Thus, this study will evaluate in healthy adults, whether the tolerability and safety profile of once daily administration of ATV-PG + AQ for 3 days supports future use in Seasonal Malaria Chemoprevention (SMC), which will entail administration on a monthly basis to an apparently healthy population of children of 3 months of age and older, for the duration of the malaria season.

This study will also determine the pharmacokinetics of ATV, PG, CG (active metabolite of PG), AQ and DEAQ (active metabolite of AQ).

Given the ultimate target population (children in Southern and Easter Africa in areas in which SMC with SPAQ is not currently deployed due to SP resistance), the study will be carried out in healthy subjects of sub-Saharan African origin (defined as subjects whose parents were both born in sub-Saharan Africa).

Conditions: Malaria
Being tested: ATV-PG 1000-400 mg + AQ 612 mg
Medical subject headings: Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ATV-PG 1000-400 mg + AQ 612 mgDrug
Also called ATV-PG 1000-400 mg + AQ unmatched placebo, ATV-PG unmatched placebo + AQ 612 mg
The dosing will be carried out by an unblinded member of the investigator's staff. Dosing will take place behind a curtain and during IMP administration the subjects will be blindfolded. ATV-PG (or placebo) will always be given first, then AQ (or placebo).

Study groups in NCT04002687
Study group	Role	What they receive
ATV-PG 1000-400 mg + AQ 612 mg	Experimental	T1 (n=16) - Atovaquone (ATV),Proguanil (PG) 1000-400 mg + Amodiaquine (AQ) 612 mg on days 1,2, 3. Receives: Drug: ATV-PG 1000-400 mg + AQ 612 mg
ATV-PG 1000-400 mg + AQ unmatched placebo	Active comparator	T 2 (n=12) - Atovaquone (ATV)-Proguanil (PG) 1000-400 mg + Amodiaquine (AQ) unmatched placebo on days 1,2, 3. Receives: Drug: ATV-PG 1000-400 mg + AQ 612 mg
ATV-PG unmatched placebo + AQ 612 mg	Active comparator	T 3 (n=12) - Atovaquone (ATV)-Proguanil (PG) unmatched placebo + Amodiaquine (AQ) 612 mg on days 1,2, 3. Receives: Drug: ATV-PG 1000-400 mg + AQ 612 mg
ATV-PG unmatched placebo + AQ unmatched placebo	Placebo comparator	T 4 (n=12) - Atovaquone (ATV)-Proguanil (PG) unmatched placebo + AQ unmatched placebo on days 1,2, 3. Receives: Drug: ATV-PG 1000-400 mg + AQ 612 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

Treatment-emergent adverse events (TEAEs) will be assessed of the approved dose of ATV-PG and the adult equivalent of the approved SMC dose of AQ when administered alone and in combination and in combination, in comparison with placebo.
TEAEs will include clinical signs, nausea, vomiting and diarrhea, proportion of subjects with clinically relevant changes in laboratory safety tests (hematology, chemistry (in particular ALT, AST and bilirubin increases) and urinalysis), proportion of subjects with morphological and/or rhythm abnormalities on electrocardiogram (ECG), proportion of subjects with clinically significant changes in ECG time intervals (PR, QRS, QT and QTc intervals) and proportion of subjects with clinically significant changes in vital signs (systolic blood pressure, diastolic blood pressure and pulse rate).
Measured: Day 1 to Day 29 post dose, (Day 36 +/- 1 day including follow up)

Secondary outcomes (6)

To measure the the maximum observed plasma concentration (Cmax) of atovaquone (ATV), proguanil (PG) and cycloguanil (CG), and amodiaquine (AQ) and desethyl-amodiaquine (DEAQ) following administration of ATV-PG and AQ alone and in combination.
To measure the maximum observed plasma concentration (Cmax).
Measured: Day 1 to Day 22
To measure the maximum plasma concentration (tmax) of atovaquone (ATV), proguanil (PG) and cycloguanil (CG), and amodiaquine (AQ) and desethyl-amodiaquine (DEAQ) following administration of ATV-PG and AQ alone and in combination.
To measure time the maximum plasma concentration (tmax).
Measured: Day 1 to Day 22
To measure the area under the plasma concentration-time curve from time zero to last detectable plasma concentration (AUC0-t) of atovaquone, proguanil and cycloguanil, and amodiaquine and desethyl-amodiaquine (DEAQ) following administration.
To measure the area under the plasma concentration-time curve from time to zero to last detectable plasmaconcentration (AUC0-t).
Measured: Day 1 to Day 22
To measure the area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of atovaquone (ATV), proguanil (PG) and cycloguanil (CG), and amodiaquine (AQ) and desethyl-amodiaquine (DEAQ) following administr
To measure the area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf)
Measured: Day 1 to Day 22
To measure the terminal elimination rate constant (λz) of atovaquone (ATV), proguanil (PG) and cycloguanil (CG), and amodiaquine (AQ) and desethyl-amodiaquine (DEAQ) following administr
To measure the terminal elimination rate constant (λz).
Measured: Day 1 to Day 22
To measure the terminal elimination half-life (t1/2) of atovaquone (ATV), proguanil (PG) and cycloguanil (CG), and amodiaquine (AQ) and desethyl-amodiaquine (DEAQ) following administr
To measure the terminal elimination half-life (t1/2).
Measured: Day 1 to Day 22

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Apr 201929 Oct 2019

First posted28 Jun 2019
Study start4 Apr 2019
Primary completion29 Oct 2019
Study completion29 Oct 2019

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.
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: Prevention
Allocation: Randomised
Intervention model: Factorial
Model description: Fifty-two subjects will be enrolled and randomized to one of the four treatment (Cohorts 1 to 4) in a ratio of 4:3:3:3 as described below: * Treatment 1 (n=16) - ATV-PG 1000-400 mg + AQ 612 mg; * Treatment 2 (n=12) - ATV-PG 1000-400 mg + AQ unmatched placebo; * Treatment 3 (n=12) - ATV-PG unmatched placebo + AQ 612 mg; * Treatment 4 (n=12) - ATV-PG unmatched placebo + AQ unmatched placebo.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 44 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04002687
Sponsor's protocol ID: APM/18/1702001
Status last verified: Mar 2020
First submitted: 17 Jun 2019
Last updated: 19 Mar 2020
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: De- Identified individual participant data for all primary and secondary outcome measures will be made available.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 19 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blind, Placebo Controlled Parallel Group Study in Heathy Adult Subjects to Determine the Tolerability and Safety of Atovaquone-proguanil (ATV-PG) Co-administered With Amodiaquine (AQ)
ClinicalTrials.gov ID: NCT04002687
Acronym / sponsor ID: APM/18/1702001
Conditions: Malaria
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 44 participants (actual)
Lead sponsor: Medicines for Malaria VentureUniversity, hospital or other
Collaborators: Richmond Pharmacology Limited
Study start: 4 Apr 2019 (actual)
Primary completion: 29 Oct 2019 (actual)
Study completion: 29 Oct 2019 (actual)
First posted: 28 Jun 2019 (actual)
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.

Detailed description

This study will also determine the pharmacokinetics of ATV, PG, CG (active metabolite of PG), AQ and DEAQ (active metabolite of AQ).

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Factorial
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4
Model description: Fifty-two subjects will be enrolled and randomized to one of the four treatment (Cohorts 1 to 4) in a ratio of 4:3:3:3 as described below: * Treatment 1 (n=16) - ATV-PG 1000-400 mg + AQ 612 mg; * Treatment 2 (n=12) - ATV-PG 1000-400 mg + AQ unmatched placebo; * Treatment 3 (n=12) - ATV-PG unmatched placebo + AQ 612 mg; * Treatment 4 (n=12) - ATV-PG unmatched placebo + AQ unmatched placebo.

Arm	Type	Receives
ATV-PG 1000-400 mg + AQ 612 mg	Experimental	Drug: ATV-PG 1000-400 mg + AQ 612 mgT1 (n=16) - Atovaquone (ATV),Proguanil (PG) 1000-400 mg + Amodiaquine (AQ) 612 mg on days 1,2, 3.
ATV-PG 1000-400 mg + AQ unmatched placebo	Active comparator	Drug: ATV-PG 1000-400 mg + AQ 612 mgT 2 (n=12) - Atovaquone (ATV)-Proguanil (PG) 1000-400 mg + Amodiaquine (AQ) unmatched placebo on days 1,2, 3.
ATV-PG unmatched placebo + AQ 612 mg	Active comparator	Drug: ATV-PG 1000-400 mg + AQ 612 mgT 3 (n=12) - Atovaquone (ATV)-Proguanil (PG) unmatched placebo + Amodiaquine (AQ) 612 mg on days 1,2, 3.
ATV-PG unmatched placebo + AQ unmatched placebo	Placebo comparator	Drug: ATV-PG 1000-400 mg + AQ 612 mgT 4 (n=12) - Atovaquone (ATV)-Proguanil (PG) unmatched placebo + AQ unmatched placebo on days 1,2, 3.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (23 listed)

1) Male or female, of sub-Saharan African origin (both parents born in sub-Saharan Africa), aged ≥18 to ≤45 years at the date of signing informed consent which is defined as the beginning of the Screening Period.
2. Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to follow the following contraception requirements. Contraception must start one complete menstrual cycle prior to the first day of dosing and continue until at least 90 days after the end of the systemic exposure of the study drug (90 days after the last study drug administration).
Female subjects who are documented as being of non-childbearing potential are exempt from contraception requirements. Documentation of non-childbearing potential must include at least one of the following criteria:
Postmenopausal - evidence of menopause based on a combination of amenorrhea for at least one year and increased serum follicle-stimulating hormone (FSH) level (> 30 IU/L), or
Surgical sterilization - evidence of hysterectomy and/or bilateral oophorectomy.

Key exclusion criteria (40 listed)

Current or recurrent disease (e.g., cardiovascular, haematological, neurological,endocrine, immunological, renal, hepatic or gastrointestinal or other conditions) that could affect the action, absorption, or disposition of ATV-PG or AQ, or could affect clinical assessments or clinical laboratory evaluations.
Any significant history of seizures or epilepsy.
Current or relevant history of physical or psychiatric illness that may require treatment or make the subject unlikely to fully comply with the requirements or complete the study, or any condition that presents undue risk from the investigational product or study procedures.
Any other significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study may influence the result of the study, or the subject's ability to participate in the study.
Documented retinopathy.

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
ATV-PG 1000-400 mg + AQ 612 mgAlso: ATV-PG 1000-400 mg + AQ unmatched placebo, ATV-PG unmatched placebo + AQ 612 mgThe dosing will be carried out by an unblinded member of the investigator's staff. Dosing will take place behind a curtain and during IMP administration the subjects will be blindfolded. ATV-PG (or placebo) will always be given first, then AQ (or placebo).	Drug	ATV-PG 1000-400 mg + AQ 612 mg, ATV-PG 1000-400 mg + AQ unmatched placebo, ATV-PG unmatched placebo + AQ 612 mg, ATV-PG unmatched placebo + AQ unmatched placebo

Primary outcome

Treatment-emergent adverse events (TEAEs) will be assessed of the approved dose of ATV-PG and the adult equivalent of the approved SMC dose of AQ when administered alone and in combination and in combination, in comparison with placebo.
Time frame: Day 1 to Day 29 post dose, (Day 36 +/- 1 day including follow up)
TEAEs will include clinical signs, nausea, vomiting and diarrhea, proportion of subjects with clinically relevant changes in laboratory safety tests (hematology, chemistry (in particular ALT, AST and bilirubin increases) and urinalysis), proportion of subjects with morphological and/or rhythm abnormalities on electrocardiogram (ECG), proportion of subjects with clinically significant changes in ECG time intervals (PR, QRS, QT and QTc intervals) and proportion of subjects with clinically significant changes in vital signs (systolic blood pressure, diastolic blood pressure and pulse rate).

6 secondary outcomes

To measure the the maximum observed plasma concentration (Cmax) of atovaquone (ATV), proguanil (PG) and cycloguanil (CG), and amodiaquine (AQ) and desethyl-amodiaquine (DEAQ) following administration of ATV-PG and AQ alone and in combination.
Time frame: Day 1 to Day 22
To measure the maximum plasma concentration (tmax) of atovaquone (ATV), proguanil (PG) and cycloguanil (CG), and amodiaquine (AQ) and desethyl-amodiaquine (DEAQ) following administration of ATV-PG and AQ alone and in combination.
Time frame: Day 1 to Day 22
To measure the area under the plasma concentration-time curve from time zero to last detectable plasma concentration (AUC0-t) of atovaquone, proguanil and cycloguanil, and amodiaquine and desethyl-amodiaquine (DEAQ) following administration.
Time frame: Day 1 to Day 22
To measure the area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of atovaquone (ATV), proguanil (PG) and cycloguanil (CG), and amodiaquine (AQ) and desethyl-amodiaquine (DEAQ) following administr
Time frame: Day 1 to Day 22
To measure the terminal elimination rate constant (λz) of atovaquone (ATV), proguanil (PG) and cycloguanil (CG), and amodiaquine (AQ) and desethyl-amodiaquine (DEAQ) following administr
Time frame: Day 1 to Day 22
To measure the terminal elimination half-life (t1/2) of atovaquone (ATV), proguanil (PG) and cycloguanil (CG), and amodiaquine (AQ) and desethyl-amodiaquine (DEAQ) following administr
Time frame: Day 1 to Day 22

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 19 Mar 2020.
Individual participant dataSharing planned: Yes. De- Identified individual participant data for all primary and secondary outcome measures will be made available.

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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.

Ulrike Lorch, MD FRCA FFPM principal investigator

Richmond Pharmacology Limited

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 ATV-PG 1000-400 mg + AQ 612 mg in people with Malaria, run by Medicines for Malaria Venture at 1 site in United Kingdom.

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 23 inclusion and 40 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 19 Mar 2020. 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 United Kingdom. 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. Some participants in this study may receive a placebo. 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?

Treatment-emergent adverse events (TEAEs) will be assessed of the approved dose of ATV-PG and the adult equivalent of the approved SMC dose of AQ when administered alone and in combination and in combination, in comparison with placebo. (time frame: Day 1 to Day 29 post dose, (Day 36 +/- 1 day including follow up)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04002687.

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 19 Mar 2020.