NCT05084651

Drug-drug Interaction Study of Ganaplacide and Lumefantrine With Itraconazole

A Phase I, Open-label, Fixed Sequence, Two-period, Crossover, Drug-drug Interaction Study to Investigate the Interaction Potential of Itraconazole on the Pharmacokinetics of Ganaplacide and Lumefantrine Combination in Healthy Participants

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

The study will assess the effect of multiple doses of itraconazole, a strong CYP3A4/5 inhibitor, on the PK of ganaplacide and lumefantrine in healthy participants. This study will provide data that is relevant for advice regarding possible concomitant medications that are inhibitors of CYP3A4/5 in future clinical studies with ganaplacide and lumefantrine and for potential future labeling considerations

Detailed description

This is an open-label, fixed sequence, 2-period, crossover, drug-drug interaction (DDI) study, to evaluate the effect of multiple doses of itraconazole on the single dose PK of ganaplacide and lumefantrine in healthy participants. The study will consist of a screening period of up to 28 days, 2 Baseline evaluations (on Day -1 of each treatment period), and 2 treatment periods which are separated by a washout period. Participants who meet the eligibility criteria at Screening will be admitted to the study site for First Baseline evaluations on Day -1 of Period 1. Baseline safety assessments will be performed prior to first dosing of study treatment in each period. Participants enrolled will receive a single oral dose of ganaplacide and lumefantrine combination on Day 1 of Period 1. In Period 2, participants will receive itraconazole once daily (q.d.) on Days 1 to 18 and a single dose of ganaplacide and lumefantrine combination on Day 5, approximately 2 hours after the itraconazole dose. There will be 336 hours of sequential blood sampling for PK assessment starting after ganaplacide and lumefantrine dosing in each treatment period. Between the 2 treatment periods, there will be an additional washout period of at least 14 days, beginning from the last PK sample collection in Period 1 and continuing until the first dose of study treatment in Period 2. Each dose of ganaplacide and lumefantrine combination will be administered after at least 10 hours of overnight fasting and will be followed by at least 4 hours of fasting post dose. In Period 2, itraconazole will be administered after at least 10 hours of overnight fasting and followed by at least 1 hour of fasting post dose (except on Day 5 when ganaplacide and lumefantrine will be administered approximately 2 hours after itraconazole dosing and participants will continue fasting for at least 4 hours post ganaplacide and lumefantrine dosing). Safety assessments (including physical examinations, electrocardiograms (ECGs), vital signs, clinical laboratory evaluations \[hematology, chemistry, coagulation, and urinalysis\], and adverse event \[AE\] and serious adverse event \[SAE\] monitoring) will be performed during the study. The Study Completion evaluations will occur on Day 19 of Period 2, followed by a post study safety contact (e.g. follow-up telephone call, email) approximately 30 days after the last dose of study treatment. In the case of early termination, Study Completion evaluations will be conducted prior to discharge from the study.

Conditions

• Malaria

Interventions

Type	Name	Description
DRUG	Ganaplacide	Treatment A/Period 1: 400 mg (4 x 100 mg tablets) at Hour 0 on Day 1 Treatment B/Period 2: 400 mg (4 x 100 mg tablets) at Hour 0, approximately 2 hours after itraconazole dosing, on Day 5.
COMBINATION_PRODUCT	Lumefantrine	Treatment A/Period 1: 480 mg (2 x 240 mg sachets) at Hour 0 on Day 1 Treatment B/Period 2: 480 mg (2 x 240 mg sachets) at Hour 0, approximately 2 hours after itraconazole dosing, on Day 5.
DRUG	Itraconazole	200 mg (20 mL of 10 mg/mL oral solution) q.d. on Days 1 to 18

Timeline

• Start date: 2021-11-18
• Primary completion: 2022-05-13
• Completion: 2022-05-14
• First posted: 2021-10-20
• Last updated: 2022-10-28

Locations

1 site across 1 country: United Kingdom