Tafenoquine Thorough QTc Study in Healthy Subjects

NCT01928914 | Completed Phase 1

• 1 other identifier: 114582
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 2

Brief Summary

This will be a randomized, single-blind, placebo controlled, parallel group study. Approximately 260 subjects will be enrolled in five groups. This study is designed to compare the effects of tafenoquine, administered as single dose as well as administered over three consecutive days, on the changes in QT duration to those observed in subjects dosed with either moxifloxacin or placebo.

Conditions

Malaria, Vivax

Outcome Measures

Primary Outcomes (1)

• Change from baseline in QTcF for 1200 mg dose of tafenoquine compared to baseline

  Contineous QTcF will be electronically recorded using holtor monitors. The primary comparison of interest is the mean time-matched change from baseline in QTcF for the difference tafenoquine-placebo for 1200mg dose of tafenoquine at each timepoint.

  Day 1, Day 2, day 3, Day 4, Day 5 and Day 6

Secondary Outcomes (8)

• Change from Baseline in QTcB, QTcI, QT, and HR for 1200mg dose of tafenoquine

  Day 1, Day 2, day 3, Day 4, Day 5 and Day 6

• Change from Baseline in QTcF QTcB, QTcI, QT, and HR for 300 mg single dose of tafenoquine

  Day 1, Day 2, day 3, Day 4, Day 5 and Day 6

• Change from Baseline in QTcF, QTcB, QTcI, QT, and HR for placebo

  Day 1, Day 2, day 3, Day 4, Day 5 and Day 6

• Change from Baseline in QTcF, QTcB, QTcI, QT, and HR for moxifloxacin

  Day 1, Day 2, day 3, Day 4, Day 5 and Day 6

• Plasma concentrations and derived pharmacokinetic parameters AUC(0-t), Cmax, and tmax of tafenoquine

  Day 1, Day 2, day 3, Day 4, Day 5 and Day 6

Study Arms (5)

Group 1

PLACEBO COMPARATOR

Subjects in group 1 receive placebo for tafenoquine and placebo for moxifloxacin on three consecutive days of dosing

Drug: Placebo for Tafenoquine; Drug: Placebo for moxifloxaxin

Group 2

EXPERIMENTAL

Subjects in group 2 receive 400mg of tafenoquine and placebo for moxifloxacin on three consecutive days of dosing

Drug: Tafenoquine 1200mg; Drug: Placebo for Tafenoquine

Group 3

ACTIVE COMPARATOR

Subjects in group 1 receive placebo for tafenoquine and placebo for moxifloxacin on days 1 and 2. On day 3, subjects receive placebo for tafenoquine and 400mg moxifloxacin.

Drug: moxifloxacin; Drug: Placebo for Tafenoquine; Drug: Placebo for moxifloxaxin

Group 4

EXPERIMENTAL

Subjects in group 1 receive placebo for tafenoquine and placebo for moxifloxacin on days 1 and 2. On day 3, subjects receive placebo for moxifloxacin and 300mg of tafenoquine

Drug: Tafenoquine 300mg; Drug: Placebo for Tafenoquine; Drug: Placebo for moxifloxaxin

Group 5

EXPERIMENTAL

Subjects in group 1 receive placebo for tafenoquine and placebo for moxifloxacin on days 1 and 2. On day 3, subjects receive placebo for moxifloxacin and 600mg of tafenoquine

Drug: Tafenoquine 600mg; Drug: Placebo for Tafenoquine; Drug: Placebo for moxifloxaxin

Interventions

Tafenoquine 300mg DRUG

Single dose of Tafenoquine give on Day 3 only

Group 4

Tafenoquine 600mg DRUG

Single dose of Tafenoquine given on Day 3 only

Group 5

Tafenoquine 1200mg DRUG

400mg Dose of Tafenoquine given on each of the three consecutive dosing days

Group 2

moxifloxacin DRUG

moxifloxacine given on Day 3 only

Group 3

Placebo for Tafenoquine DRUG

Placebo given on all three days to all groups except for group 5 on Day 3

Group 1; Group 2; Group 3; Group 4; Group 5

Placebo for moxifloxaxin DRUG

Placebo for moxifloxacin, given to all groups on all days except for Group 3 on Day 3

Group 1; Group 3; Group 4; Group 5

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and baseline ECG cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
• 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; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<147 pmol/L) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in the protocol 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 enrollment. 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 and agrees to use one of the contraception methods listed in Section 8.1 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 90 days post-last dose.
• Body weight ≥50 kg for men and ≥45 kg for women and BMI within the range 18.5 to 31.0 kg/m2 (inclusive).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

You may not qualify if:

• Documented Glucose-6-phosphate dehydrogenase (G6PD) deficiency, determined by a quantitative assay of enzyme activity.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• 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 thalassaemia; or current or past history of methemoglobinemia or methemoglobin percentage above the reference range at screening.
• A positive pre-study drug/alcohol screen.
• A positive test for HIV antibody.
• History of 2nd degree or higher AV block.
• Donation of blood or blood products in excess of 500 mL within a 56 day period prior to enrolment.
• Subjects with a hemoglobin values outside the normal range. A single repeat is allowed for eligibility determination.
• The subject's systolic blood pressure is outside the range of 90-140mmHg, or diastolic blood pressure is outside the range of 45-90mmHg or heart rate is outside the range of 50-100bpm for female subjects or 45-100 bpm for male subjects.
• PR Interval \<120 and \>220 msec
• QRS Duration \<70 and \>120 msec
• QTc, QTcB or QTcF Interval \>450 msec
• Heart Rate, for male subjects \<45 and \>100 bpm, and for female subjects \<50 and \>100 bpm
• Evidence of previous myocardial infarction (Does not include ST segment changes associated with repolarization).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Culver City, California, 90232, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

Related Links

• Results for study 114582 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Malaria, Vivax

Interventions

tafenoquine; Moxifloxacin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2012
• First Posted: August 27, 2013
• Study Start: July 26, 2011
• Primary Completion: June 4, 2012
• Study Completion: June 4, 2012
• Last Updated: June 12, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

US (2)