A Study to Assess the Effects of Dissolution Profile on the Pharmacokinetics of Single Oral Doses of Tafenoquine Tablets and Tafenoquine Stable Isotope Labelled Solution

NCT02751294 | Completed Phase 1

• 1 other identifier: 201780
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the effect of Tafenoquine (TQ) 150 mg tablet ageing (dissolution profiles) on human exposure of TQ comparing the relative bioavailability of TQ from tablets exhibiting different dissolution profiles in healthy subjects. This is a single-centre, 2-arm, randomized open-label, parallel-group study in healthy subjects. All subjects will arrive in the unit approximately 24 hours prior to dosing and will be discharged after the 72-hour post-dose assessments are completed. Subjects will return for outpatient visits on Days 7, 14, 21, 28, and 56 after dosing. A total of 14 subjects (n=7 subjects in each arm) are planned to be enrolled. All subjects will receive a single dose of study medication (2x150 mg TQ tablets + 30 mg TQ SIL in solution) and participate through a 56-day post dose follow-up visit. To enable the application of peripheral microsampling in planned paediatric studies, a comparison of the measured pharmacokinetic (PK) exposure via peripheral blood collection (via microsampling) to venous collection will also be performed in this study.

Conditions

Malaria, Vivax

Keywords

Healthy Volunteer; Malaria; Pharmacokinetics; Tafenoquine

Outcome Measures

Primary Outcomes (1)

• Ratio of the geometric means for the area under plasma concentration-time curve (AUC) for Tafenoquine X

  Blood samples for PK analysis of TQ will be collected for evaluation of ratio of the geometric means (90% Confidence Interval \[CI\]) for the area under plasma concentration-time curve from 0 to time t (AUC \[0-t\]) and area under the concentration-time curve from 0 to infinity (AUC\[0-inf\]) for the treatment group dissolution profile X compared to Control.

  Samples will be collected at Pre-dose and 1, 2, 6, 9, 12, 15, 20, 24, 36, 48, 60, and 72 hours post dose on Day 1 and single sample on Day 7, 14, 21, 28, and 56

Secondary Outcomes (11)

• Safety as assessed by clinical monitoring of blood pressure

  Up to 12 hours

• Safety as assessed by clinical monitoring of pulse rate

  Up to 12 hours

• Safety as assessed by clinical monitoring of electrocardiogram (ECGs)

  Day -1

• Safety as assessed by clinical monitoring of Haematology parameters

  Up to Day 14

• Safety as assessed by clinical monitoring of Clinical Chemistry parameters

  Up to Day 14

Study Arms (2)

TQ Control+ TQ SIL

EXPERIMENTAL

Subjects received TQ Control product (2 tablets) and 30 mg TQ SIL solution orally with water after a meal.

Drug: Tafenoquine Control; Drug: Tafenoquine SIL

TQ X + TQ SIL

EXPERIMENTAL

Subjects received 2 tablets of Tafenoquine dissolution profile X and 30 mg TQ SIL solution orally with water after a meal.

Drug: Tafenoquine dissolution profile X; Drug: Tafenoquine SIL

Interventions

Tafenoquine Control DRUG

It will be supplied as a dark pink, capsule-shaped, film-coated tablet plain on both sides containing 150 mg tafenoquine

TQ Control+ TQ SIL

Tafenoquine dissolution profile X DRUG

It will be supplied as a dark pink, capsule-shaped, film-coated tablet plain on both sides containing 150 mg tafenoquine and will be "intermediate aged TQ Product".

TQ X + TQ SIL

Tafenoquine SIL DRUG

It will be compounded at site and will be administered as 0.3 mg/mL (100mL to be dosed, equivalent to 30 mg) aqueous Solution of SIL Tafenoquine.

TQ Control+ TQ SIL; TQ X + TQ SIL

Eligibility Criteria

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

You may qualify if:

• Between 18 and 55 years of age inclusive, at the time of signing the informed consent
• Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.

You may not qualify if:

• Subject values outside the normal range should always be excluded from enrolment.
• Body weight between \>=35 kilogram (kg) and \<=100 kg.
• Male subjects only.
• Capable of giving signed informed consent as described in study protocol, which includes compliance with the requirements and restrictions listed in the consent form and in the study protocol
• Alanine Aminotransferase (ALT) and bilirubin \>1.5x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• QT interval corrected for heart rate according to Fridericia's formula (QTcF) \> 450 millisecond (msec) Note: The QTc is the QTcF). Other calculation methods (e.g. QT interval corrected using Bazett's formula \[QTcB\], QTcF) machine-read or manually over-read are not acceptable.
• Use of prescription (except acetaminophen at doses of 2 grams/day) 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.
• History of regular alcohol consumption within 30 days of the study defined as: an average weekly intake of \>14 drinks for males. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces (360 millilitre \[mL\]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
• Positive results for drugs of abuse as mentioned in protocol.
• Cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 30 days prior to screening.
• History of sensitivity to TQ, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
• History of thalassaemia; or current or past history of methemoglobinemia or methemoglobin percentage above the reference range at screening.
• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
• A positive pre-study drug/alcohol screen.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Medicines for Malaria Venture: collaborator
• Parexel: collaborator

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

Related Publications (1)

• Goyal N, Mohamed K, Rolfe K, Sahota S, Ernest T, Duparc S, Taylor M, Casillas L, Koh GCKW. Application of the Stable Isotope Label Approach in Clinical Development-Supporting Dissolution Specifications for a Commercial Tablet Product with Tafenoquine, a Long Half-life Compound. AAPS J. 2018 Jun 4;20(4):74. doi: 10.1208/s12248-018-0234-5.

  PMID: 29869298 DERIVED

MeSH Terms

Conditions

Malaria, Vivax; Malaria

Condition Hierarchy (Ancestors)

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

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 21, 2016
• First Posted: April 26, 2016
• Study Start: May 1, 2016
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: January 20, 2017

Record last verified: 2017-01

Locations

US (1)