NCT05947604

DDI Study of Single Oral Dose of Acoziborole With Sequential Co-administration of Midazolam and Dextromethorphan

Single Centre Open-label, Non-randomised, 3-treatment, 2-period, Pharmacokinetic Drug Interaction Study of Single Oral Dose of Acoziborole With Sequential Co-administration of Midazolam and Dextromethorphan in Healthy Male Participants

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Drugs for Neglected Diseases · Academic / Other
• Sex: Male
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

To assess Drug drug interactions between Acoziborole and Dextromethorphan and Midazolam in healthy male volunteers.

Detailed description

An in silico PB-PK model was developed within the simCYP software and qualified for acoziborole. This study suggested strong interactions with sensitive index substrates of CYP2D6 and CYP3A4.To validate these PB-PK model results, an open-label, non-randomised, three-treatment, one-sequence, two successive periods study with at least 3-day washout between periods was chosen to evaluate clinically the potential impact of acoziborole on plasma exposure of two different sensitive CYP substrates, DXM for CYP2D6 and midazolam for CYP3A4. Acoziborole will be administered as a single dose, due to the long t1/2 of 360 h in healthy participants. The SimCYP simulations showed that the best compromise to maximize the CYP2D6 inhibition and minimize the CYP3A4 induction is when DXM is given 24 to 60 h after acoziborole administration. Therefore, dextromethorphan will be given on Day 1 (in Period 1, without acoziborole) and on Day 14 in Period 2 i.e. 2 days following oral administration of acoziborole. Based on the PB-PK simulations, the interaction between acoziborole and midazolam should be maximal around Day 8 (due to the activity CYP3A4) following acoziborole administration and sustained for several weeks after. Thus, midazolam will be given on Day 8 (in Period 1 without acoziborole) and on Day 21 in Period 2 i.e. 9 days following oral single administration of acoziborole.

Conditions

• Trypanosomiasis, African

Interventions

Type	Name	Description
DRUG	Acoziborole	Acoziborole 960 mg (three tablets of 320 mg) for oral route in fasted condition Period 2: single oral administration on Day 12
DRUG	Midazolam	• Midazolam 5 mg syrup in fasted condition Period 1: Single oral dose of 5 mg administered on Day 8 Period 2: Single oral dose of 5 mg administered on Day 21
DRUG	Dextromethorphan	• Dextromethorphan 15 mg syrup in fasted condition Period 1: Single oral dose of 15 mg administered on Day 1 Period 2: Single oral dose of 15 mg administered on Day 14

Timeline

• Start date: 2023-02-09
• Primary completion: 2023-05-03
• Completion: 2023-05-03
• First posted: 2023-07-17
• Last updated: 2023-07-17

Locations

1 site across 1 country: Malaysia