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Malaria, VivaxPhase 1NCT02184637

A Study to Evaluate the Pharmacokinetics of a Single Dose of Tafenoquine Co-administered With Either Artemether + Lumefantrine or Dihydroartemisinin + Piperaquine Tetraphosphate

A Phase 1 study testing Tafenoquine, Dihydroartemisinin + Piperaquine tetraphosphate and Artemether + Lumefantrine in people with Malaria, Vivax, run by GlaxoSmithKline at 1 site in United States.

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

This will be a single-centre, 5-cohort, randomized open-label, parallel-group study in healthy volunteer subjects. This study aims to provide sufficient pharmacokinetic (PK) evidence to support the safe usage of Tafenoquine (TQ) in studies and markets where the Artemisinin-based Combination Therapies (ACTs) are the… Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Malaria, Vivax
What is being tested?
Tafenoquine, Dihydroartemisinin + Piperaquine tetraphosphate and Artemether + Lumefantrine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 siteUnited States
Study dates
31 Jul 2014to 8 Apr 2015
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 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s), which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator and GlaxoSmithKline (GSK) Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. Subjects whose laboratory values are outside the normal ranges will be excluded from enrolment.
  • Male or female aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • Alanine Aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5x Upper Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • QTcF <440 milliseconds (msec) based on averaged corrected QT interval (QTc) values of triplicate electrocardiogram (ECGs) obtained over a brief recording period at screening and no history of additional risk factors for Torsades des Pointes (e.g., heart failure or family history of Long QT Syndrome).
  • A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy [for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 milli-international units per (MIU)/ millilitre (mL) and estradiol <40 picograms (pg)/mL (<147 picomoles (pmol)/liter [L]) is confirmatory]. [Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods, if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.]; Child-bearing potential with negative pregnancy test as determined by serum or urine human chorionic gonadotropin (hCG) test at screening or prior to dosing AND Agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 56-days post first dose. OR has only same-sex partners, when this is her preferred and usual lifestyle.
  • Body Mass Index (BMI) within the range 18.5 to 31.0 kilogram/square meter (kg/m^2) (inclusive) and body weight between >=36kilogram (kg) and <=100kg.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Who cannot join

  • The subject's average triplicate (at screening after approximately 5 minutes at rest in the semi-supine position) systolic blood pressure is outside the range of 80-140 millimeters of mercury (mmHg), or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 40-100 beats per minute (bpm).
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
  • Lactating females.
  • Criteria Based Upon Medical Histories:
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
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  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • History of thalassaemia; or current or past history of methemoglobinemia or methemoglobin percentage above the reference range at screening.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Consumption of Seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, or grapefruit hybrids from 7 days prior to the first dose of study medication.
  • Use of prescription (except female contraception) or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • Criteria Based Upon Diagnostic Assessments:
  • Subjects with a haemoglobin values outside the lower limit of normal range. A single repeat is allowed for eligibility determination.
  • Documented phenotypic Glucose-6-phosphate dehydrogenase (G6PD) deficiency, determined by a quantitative assay of enzyme activity. Defined as <70% of locally defined median.
  • Potassium <4.0 millimoles (mmol)/L and Magnesium <1.8 mg/ deciliter (dL). Subjects with potassium (K) and magnesium (Mg) values below these screening or on Day-1 may be treated with oral supplementation and be retested for eligibility prior to dosing.
  • Cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 30 days prior to screening.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  • A positive pre-study drug/alcohol screen.
  • A positive test for human immunodeficiency virus (HIV) antibody.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • GSK Investigational Site

    Baltimore, Maryland, 21225

Other trials in United States

About this study

Official title: A Five-cohort, Randomized, Open-label, Parallel-group Study to Evaluate the Pharmacokinetics of a Single Dose of Tafenoquine (SB252263) 300mg When Co-administered With the Artemisinin-based Combination Therapies (ACT) Artemether + Lumefantrine (AL) and Dihydroartemisinin + Piperaquine Tetraphosphate (DHA+PQP)

This will be a single-centre, 5-cohort, randomized open-label, parallel-group study in healthy volunteer subjects. This study aims to provide sufficient pharmacokinetic (PK) evidence to support the safe usage of Tafenoquine (TQ) in studies and markets where the Artemisinin-based Combination Therapies (ACTs) are the standard of care for patients with Plasmodium vivax malaria (i.e., co administration with TQ). The objective of this study is to assess the pharmacokinetics, safety and tolerability of TQ when co-administered with the chosen ACTs (AL and DHA + PQP), administered concomitantly in healthy subjects. Specifically, the study will evaluate whether there are drug-drug interactions between TQ and each of the ACTs and if these interactions are considered to be clinically significant. The co-primary objectives of this study are to characterize both the effects of a 300 milligram (mg) single dose of TQ on the pharmacokinetics; changes in (area under the concentration-time curve from 0 to time t) AUC (0-t), AUC (0-infinity), and maximum observed concentration (Cmax) of each of the two Artemisinin-based Combination Therapies (ACT) according to their prescribed dose when co-administered as well as the effects of the ACTs on the PK of TQ.

A total of 120 subjects (24 subjects in each of 5 cohorts) are planned to be enrolled in order to ensure a target sample size of at least 22 subjects completing the study per cohort. All subjects will arrive in the unit at least 24 hours prior to dosing and be discharged after 72-hour post first dose assessments have been completed. Subjects will return for outpatient visits on Days 7, 14, 21, 28, and 56 after first dose.

Conditions
Malaria, Vivax
Being tested
Tafenoquine, Dihydroartemisinin + Piperaquine tetraphosphate, Artemether + Lumefantrine
Keywords
Malaria, Artemisinin-based Combination Therapies (ACT)
Medical subject headings
Malaria, Vivax, Malaria

What participants receive

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

  • TafenoquineDrug

    A dark pink, capsule-shaped, film-coated tablet containing 150mg tafenoquine. To be administered orally

  • Dihydroartemisinin + Piperaquine tetraphosphateDrug

    White, oblong, biconvex, film-coated tablet with a break-line and marked on one side with two "σ" letters containing 320 mg piperaquine tetraphosphate (as the tetrahydrate; PQP) and 40 mg dihydroartemisinin (DHA). To be administered orally

  • Artemether + LumefantrineDrug

    Light yellow, round tablet with "NC" debossed on one side and "CG" on the other, containing 20 mg artemether and 120 mg lumefantrine. To be administered orally

Study groups in NCT02184637
Study groupRoleWhat they receive
Cohort 1- TQ w/DHA+PQPExperimentalTafenoquine (TQ) will be co-administered with Dihydroartemisinin + Piperaquine tetraphosphate (DHA+PQP) on Day 1. DHA+PQP alone will be administered at 24 hours (h) (Day 2) and 48 h (Day 3) post first dose administration.
Receives: Drug: Tafenoquine; Drug: Dihydroartemisinin + Piperaquine tetraphosphate
Cohort 2 - TQ w/ALExperimentalTafenoquine co-administered with Artemether + Lumefantrine (AL) on Day 1. AL alone will be administered at 8h (Day 1), 24h and 36h (Day 2), 48h and 60 h (Day 3) post first dose administration.
Receives: Drug: Tafenoquine; Drug: Artemether + Lumefantrine
Cohort 3 - DHA+PQP aloneExperimentalDihydroartemisinin + Piperaquine tetraphosphate (DHA+PQP) will be administered on Day 1 and at 24 hours (Day 2) and 48 hours (Day 3) post first dose administration
Receives: Drug: Dihydroartemisinin + Piperaquine tetraphosphate
Cohort 4 - AL aloneExperimentalArtemether + Lumefantrine will be administered on Day 1 and 8h, 24 and 36h (Day 2), 48h and 60 h(Day 3) post first dose administration
Receives: Drug: Artemether + Lumefantrine
Cohort 5 - TQ aloneExperimentalA single dose of Tafenoquine will be administered on Day 1
Receives: Drug: Tafenoquine

What is being measured

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

  1. Ratios of Geometric mean (90% [confidence interval] CI) for DHA+PQP AUC and Cmax for treatment groups: Cohort 1 (TQ + DHA+PQP) versus (vs.) cohort 3 (DHA+PQP)

    Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 48.5, 49, 49.5, 50, 51, 52, 54, 56, 60 hours), Day 4 (72 hours), Days 7, 14, 21, 28 and 56.

    Measured: Up to Day 56

  2. Ratios of geometric mean [90% CI] for A/DHA/L AUC and Cmax for treatment groups: Cohort 2 (TQ + AL) vs. cohort 4 (AL).

    Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 60, 60.5, 61, 61.5, 62, 64 hours), Day 4 (66, 68, 72 hours), Days 7, 14, 21, 28 and 56.

    Measured: Up to Day 56

  3. Ratios of geometric mean [90% CI] for TQ AUC and Cmax for treatment groups: Cohort 1 (TQ + DHA+PQP) vs. cohort 5 (TQ).

    Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 48.5, 49, 49.5, 50, 51, 52, 54, 56, 60 hours), Day 4 (72 hours), Days 7, 14, 21, 28 and 56.

    Measured: Up to Day 56

  4. Ratios of geometric mean [90% CI] for TQ AUC and Cmax for treatment groups: Cohort 2 (TQ + AL) vs. cohort 5 (TQ).

    Blood samples will be collected on Day 1 (Pre-dose, 1, 2, 4, 6, 12 hours), Day 2 (24 hours), Day 3 (48, 60, 60.5, 61, 61.5, 62, 64 hours), Day 4 (66, 68, 72 hours), Days 7, 14, 21, 28 and 56.

    Measured: Up to Day 56

Secondary outcomes (6)

  1. Pharmacokinetic endpoints including changes in time to Cmax (Tmax) and apparent terminal phase half-life (t½) for TQ, as data permit.

    Measured: Up to Day 56

  2. Pharmacokinetic endpoints including changes in Tmax and t½ for each of the ACTs, as data permit.

    Measured: Up to Day 56

  3. Changes in safety laboratory measures (including haemoglobin change from baseline [mean of pre-dose and Day-1 results])

    Laboratory assessments will include haematology, clinical chemistry and urinalysis.

    Measured: Day -1 to Day 28

  4. Frequency of adverse events (AEs)

    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    Measured: Day -1 to Day 56

  5. Maximum change from baseline in QT interval corrected for heart rate by Fridericia's formula (QTcF) for all cohorts

    The baseline measurement will be the average of the triplicate measurements taken on pre-dose Day 1.

    Measured: Day 1 to Day 56

  6. Change from baseline in QTcF at 52-hours post-first dose for subjects who receive DHA+PQP (cohort 1 and 3)

    The baseline measurement will be the average of the triplicate measurements taken on pre-dose Day 1.

    Measured: Pre-dose (Day 1) and 52-hours post-dose ( Day 3)

Timeline

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

  1. First posted9 Jul 2014 (estimated)
  2. Study start31 Jul 2014
  3. Primary completion8 Apr 2015
  4. Study completion8 Apr 2015

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02184637
Sponsor's protocol ID
200951
Status last verified
Jul 2017
First submitted
3 Jul 2014
Last updated
13 Jul 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • Green JA, Mohamed K, Goyal N, Bouhired S, Hussaini A, Jones SW, Koh GC, Kostov I, Taylor M, Wolstenholm A, Duparc S. Pharmacokinetic Interactions between Tafenoquine and Dihydroartemisinin-Piperaquine or Artemether-Lumefantrine in Healthy Adult Subjects. Antimicrob Agents Chemother. 2016 Nov 21;60(12):7321-7332. doi: 10.1128/AAC.01588-16. Print 2016 Dec.

    PubMed 27697758

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tafenoquine, Dihydroartemisinin + Piperaquine tetraphosphate and Artemether + Lumefantrine in people with Malaria, Vivax, run by GlaxoSmithKline at 1 site in United States.

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 7 inclusion and 21 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 13 Jul 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 United States. 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?

Ratios of Geometric mean (90% [confidence interval] CI) for DHA+PQP AUC and Cmax for treatment groups: Cohort 1 (TQ + DHA+PQP) versus (vs.) cohort 3 (DHA+PQP) (time frame: Up to Day 56). The study lists 4 primary outcomes in all. 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 NCT02184637, which also lists 1 linked publication.

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 13 Jul 2017.

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