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

Phase 1

Completed

• Conditions: Trypanosomiasis, African
• Interventions: Drug: Acoziborole; Drug: Dextromethorphan; Drug: Midazolam

• Registration Number: NCT05947604
• Lead Sponsor: Drugs for Neglected Diseases

Brief 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.

Study Timeline

• Study Start: 2023-02-09
• Study First Submitted: 2023-03-05
• Primary Completion: 2023-05-03
• Study Completion: 2023-05-03
• Status Verified: 2023-06
• Study First Submitted QC: 2023-07-07
• Last Update Submitted: 2023-07-07
• Study First Posted: 2023-07-17
• Last Update Posted: 2023-07-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 20

Inclusion Criteria

• Healthy males.
• Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures..
• Age 18 to 55 (inclusive) years of age at the time of signing informed consent.
• Body mass index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening.
• Body weight not less than 50 kg.
• Non-smokers (defined as has not used nicotine-containing products including e-cigarette for at least 3 months prior to the first dose as confirmed by cotinine test).
• Must be willing and able to communicate and participate in the whole study.
• Normal blood pressure (BP): Systolic BP (SBP) between 90 and 140 mmHg (inclusive), diastolic BP (DBP) between 45 and 90 mmHg (inclusive), measured after 10 min rest in supine position at screening and first admission (Day -1).
• A resting heart rate (HR) between 45 and 90 bpm (inclusive), measured after 10 min rest in supine position at screening and first admission (Day -1).
• ECG recording without clinically significant abnormality, including Fridericia's corrected interval between Q and T waves (QTcF) measure of ≤450 msec at screening and first admission (Day -1).
• Participants must be able to swallow multiple capsules.

Exclusion Criteria

• Have participated in an investigational trial involving administration of any investigational compound within 90 days prior to the study dosing or 5-times the half-life of the drug tested in the previous clinical trial, whichever is longer (time calculated relative to the last dose in the previous clinical trial).
• History of any drug or alcohol abuse in the past 2 years.
• Regular alcohol consumption >14 units per week and (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type) as confirmed by a positive alcohol breath test at screening or any on admission to the CRW.
• Participants who do not have suitable veins for multiple venepunctures/cannulations as assessed by the Investigator or delegate at screening.
• Clinically significant abnormal clinical chemistry, haematology, urinalysis, or clinically significant abnormal physical examination findings as judged by the Investigator.
• Abnormal renal function (estimate glomerular filtration rate [eGFR] <90 mL/min).
• Confirmed positive drugs of abuse urine test result (including but not limited to, amphetamines, tetrahydrocannabinol, morphine, methamphetamine, ketamine and benzodiazepines) and at any time during the study.
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results.
• Positive COVID test at screening and at admission of hospitalisation.
• COVID-19 full vaccination to be received less than 21 days before Day 1, or start of vaccination, or second dose or booster of vaccination planned during the study period.
• Clinically significant medical condition and/or abnormal laboratory results that could, in the opinion of the Investigator, jeopardize the participant's safety or participation in the study.
• Known serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients in the past.
• Presence or history of clinically significant allergy requiring treatment (including asthma, urticaria, clinically significant allergic rash or other severe allergic diathesis), as judged by the Investigator. Hay fever is allowed unless it is active.
• Donation or loss of greater than 400 mL of blood within the previous 3 months or more than 100 mL within 30 days before signing informed consent form (ICF) to this trial.
• Participants who are taking any prescribed drug in the 30 days before screening or require regular use of any prescription medication during the study.
• Participants who have taken, any OTC medications, including vitamins, analgesics or antacids, herbal remedies, St. John's wort or diet complements (plants and vitamins that may be used for e.g. weight control or improve digestion or for "detox"... e.g., found in the composition extracts of ginkgo biloba, aesculus, cassia, harpagophytum, curcuma, elderberry, Vitis vinifera, cypress (Cupressus sempervirens)) in the 30 days before investigational medicinal product (IMP) administration. Exceptions may apply on a case-by-case basis, if considered not to interfere with the objectives of the study, as determined by the Principal Investigator (PI).
• Use of enzyme-altering drugs (e.g. barbiturates, phenothiazines, cimetidine) within 30 days or 5 half-lives, whichever is longer, of study Day 1.
• Use of products containing quinine (e.g., tonic water), grapefruit products, pomelo products, Seville orange products, supplements containing citrus aurantium and bitter orange in the 30 days prior to study Day 1.
• CYP2D6 poor metabolizers, based on genotyping of DNA from blood samples.
• Surgery within 12 weeks prior to screening, with the exception of appendectomy or at the discretion of the Investigator for minor surgery.
• Any surgery (e.g. gastric bypass) or medical condition that may affect absorption of orally administered drugs.
• Failure to satisfy the Investigator of fitness to participate for any other reason.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Dextromethorphan and Midazolam	Dextromethorphan	Drug drug interaction Dextromethorphan and Midazolam administrations * Dextromethorphan 15 mg syrup in fasted condition Period 1: Single oral dose of 15 mg administered on Day 1 * Midazolam 5 mg syrup in fasted condition Period 1: Single oral dose of 5 mg administered on Day 8
Acoziborole, Dextromethorphan and Midazolam	Midazolam	Drug drug interaction Acoziborole, Dextromethorphan and Midazolam administrations * Acoziborole 960 mg (three tablets of 320 mg) for oral route in fasted condition Period 2: single oral administration on Day 12 * Dextromethorphan 15 mg syrup in fasted condition Period 2: Single oral dose of 15 mg administered on Day 14 * Midazolam 5 mg syrup in fasted condition Period 2: Single oral dose of 5 mg administered on Day 21
Dextromethorphan and Midazolam	Midazolam	Drug drug interaction Dextromethorphan and Midazolam administrations * Dextromethorphan 15 mg syrup in fasted condition Period 1: Single oral dose of 15 mg administered on Day 1 * Midazolam 5 mg syrup in fasted condition Period 1: Single oral dose of 5 mg administered on Day 8
Acoziborole, Dextromethorphan and Midazolam	Acoziborole	Drug drug interaction Acoziborole, Dextromethorphan and Midazolam administrations * Acoziborole 960 mg (three tablets of 320 mg) for oral route in fasted condition Period 2: single oral administration on Day 12 * Dextromethorphan 15 mg syrup in fasted condition Period 2: Single oral dose of 15 mg administered on Day 14 * Midazolam 5 mg syrup in fasted condition Period 2: Single oral dose of 5 mg administered on Day 21
Acoziborole, Dextromethorphan and Midazolam	Dextromethorphan	Drug drug interaction Acoziborole, Dextromethorphan and Midazolam administrations * Acoziborole 960 mg (three tablets of 320 mg) for oral route in fasted condition Period 2: single oral administration on Day 12 * Dextromethorphan 15 mg syrup in fasted condition Period 2: Single oral dose of 15 mg administered on Day 14 * Midazolam 5 mg syrup in fasted condition Period 2: Single oral dose of 5 mg administered on Day 21

Primary Outcome Measures

Name	Time	Method
To assess the effect of single dose of acoziborole on pharmacokinetics (PK) parameters (Cmax) of dextromethorphan as a probe substrate for CYP2D6 (inhibition).	Up to 72 hours post drug administration	Dextromethorphan Cmax, plasma concentration
To assess the effect of single dose of acoziborole on pharmacokinetics (PK) parameters ( AUC0-t) of midazolam as a probe substrate for CYP3A4 (induction)	Up to 72 hours post drug administration	Midazolam AUC0-t (plasma concentration) of Period 1 and Period 2.
To assess the effect of single dose of acoziborole on pharmacokinetics (PK) parameters (AUC0-24) of midazolam as a probe substrate for CYP3A4 (induction)	Up to 72 hours post drug administration	Midazolam AUC0-24 (plasma concentration) of Period 1 and Period 2
To assess the effect of single dose of acoziborole on pharmacokinetics (PK) parameters (Cmax) of midazolam as a probe substrate for CYP3A4 (induction)	Up to 72 hours post drug administration	Midazolam Cmax, plasma concentration
To assess the effect of single dose of acoziborole on pharmacokinetics (PK) parameters (AUC0-24) of dextromethorphan as a probe substrate for CYP2D6 (inhibition).	Up to 72 hours post drug administration	Dextromethorphan AUC0-24 of Period 1 and Period 2.
To assess the effect of single dose of acoziborole on pharmacokinetics (PK) parameters ( AUC0-t) of dextromethorphan as a probe substrate for CYP2D6 (inhibition).	Up to 72 hours post drug administration	Dextromethorphan AUC0-t (plasma concentration) of Period 1 and Period 2.

Secondary Outcome Measures

Name	Time	Method
To evaluate the clinical safety of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone: ear body temperature	Up to End of Study (Day 28 to Day 31)	Vital signs for safety monitoring: ear body temperature (°C).
To evaluate the clinical safety of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone: 12-lead ECG RR Interval	Up to Day 22	12-lead electrocardiogram (ECG) RR Interval for safety monitoring purpose. ECGs for safety purpose will be performed using the internationally recognized 12 leads with devices recorder after 10 min rest in supine position and before any blood draws. ECG will be recorded at a standard paper speed of 25 mm/s and gain of 10 mm/mV. Print-outs for each ECG will include: date, time, initials of the Investigator or its deputy.; The ECGs will be performed in 6 × 2 leads during this study. The corresponding source data will consist of the ECG recorder paper print-outs.; The ECGs will be read and analysed by the Investigator.
To evaluate the clinical safety of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone: 12-lead ECG QRS duration	Up to Day 22	12-lead electrocardiogram (ECG) QRS duration for safety monitoring purpose. ECGs for safety purpose will be performed using the internationally recognized 12 leads with devices recorder after 10 min rest in supine position and before any blood draws. ECG will be recorded at a standard paper speed of 25 mm/s and gain of 10 mm/mV. Print-outs for each ECG will include: date, time, initials of the Investigator or its deputy.; The ECGs will be performed in 6 × 2 leads during this study. The corresponding source data will consist of the ECG recorder paper print-outs.; The ECGs will be read and analysed by the Investigator.
To evaluate the laboratory safety, K+, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, K+, from baseline to EoS visit.
To evaluate the clinical safety of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone: Height	Baseline	Vital signs for safety monitoring: Height (cm)
To evaluate the clinical safety of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone: respiratory rate	Up to End of Study (Day 28 to Day 31)	Vital signs for safety monitoring: respiratory rate (breaths/minute)
To evaluate the laboratory safety, mean corpuscular volume, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, mean corpuscular volume, from baseline to EoS visit.
To evaluate the clinical and laboratory safety of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to End of Study Visit, Day 31	Frequency and cumulative incidence of treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs) from time of first IMP administration (dextromethorphan on Day 1 in Period 1) to EoS visit.
To evaluate the clinical safety of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone: weight	Baseline and End of Study (Day 28 to Day 31)	Vital signs for safety monitoring: Weight (Kgs)
To evaluate the laboratory safety, Red blood cell count, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, Red blood cell count, from baseline to EoS visit.
To evaluate the laboratory safety, red cell distribution width, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, red cell distribution width, from baseline to EoS visit.
To evaluate the clinical safety of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone: Sistolic and Diastolic BP	Up to End of Study (Day 28 to Day 31)	Vital signs for safety monitoring: Sistolic BP and Diastolic BP (mmHg)
To evaluate the clinical safety of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone: 12-lead ECG Heart Rate	Up to Day 22	12-lead electrocardiogram (ECG) Heart Rate for safety monitoring purpose. ECGs for safety purpose will be performed using the internationally recognized 12 leads with devices recorder after 10 min rest in supine position and before any blood draws. ECG will be recorded at a standard paper speed of 25 mm/s and gain of 10 mm/mV. Print-outs for each ECG will include: date, time, initials of the Investigator or its deputy.; The ECGs will be performed in 6 × 2 leads during this study. The corresponding source data will consist of the ECG recorder paper print-outs.; The ECGs will be read and analysed by the Investigator.
To evaluate the laboratory safety, hematocrit, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, hematocrit, from baseline to EoS visit.
To evaluate the laboratory safety, basophils, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, basophils, from baseline to EoS visit.
To evaluate the laboratory safety, indirect bilirubin, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, indirect bilirubin, from baseline to EoS visit.
To evaluate the laboratory safety, albumin, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, albumin, from baseline to EoS visit.
To evaluate the apparent terminal elimination half-life of dextromethorphan, when co-administered with acoziborole.	Up to Day 22	Apparent terminal elimination half-life (t½) for dextromethorphan.
To evaluate the AUC0-∞ of dextromethorphan when co-administered with acoziborole.	Up to Day 22	AUC0-∞ for dextromethorphan.
To evaluate the clinical safety of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone: 12-lead ECG QT-interval	Up to Day 22	12-lead electrocardiogram (ECG) QT-interval for safety monitoring purpose. ECGs for safety purpose will be performed using the internationally recognized 12 leads with devices recorder after 10 min rest in supine position and before any blood draws. ECG will be recorded at a standard paper speed of 25 mm/s and gain of 10 mm/mV. Print-outs for each ECG will include: date, time, initials of the Investigator or its deputy.; The ECGs will be performed in 6 × 2 leads during this study. The corresponding source data will consist of the ECG recorder paper print-outs.; The ECGs will be read and analysed by the Investigator.
To evaluate the laboratory safety, monocytes, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, monocytes, from baseline to EoS visit.
To evaluate the laboratory safety, platelet count, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, platelet count, from baseline to EoS visit.
To evaluate the laboratory safety, ALP, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, ALP, from baseline to EoS visit.
To evaluate the laboratory safety, AST, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, AST, from baseline to EoS visit.
To evaluate the laboratory safety, CPK, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, CPK, from baseline to EoS visit.
To evaluate the laboratory safety, fasting glucose, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, fasting glucose, from baseline to EoS visit.
To evaluate the laboratory safety, urea, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, urea, from baseline to EoS visit.
To evaluate the laboratory safety, Na+, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, Na+, from baseline to EoS visit.
To evaluate the laboratory safety, Cl-, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, Cl-, from baseline to EoS visit.
To evaluate the Tmax of midazolam when co-administered with acoziborole.	Up to Day 22	Time to maximum observed plasma concentration (tmax) for midazolam
To evaluate the Cmax of midazolam's metabolite, 1'hydroxy-midazolam, when co-administered with acoziborole.	Up to Day 22	1'-hydroxy-midazolam: Cmax for Period 1 and Period 2.
To evaluate the Tmax of midazolam's metabolite, 1'hydroxy-midazolam, when co-administered with acoziborole.	Up to Day 22	1'-hydroxy-midazolam: tmax for Period 1 and Period 2.
To evaluate the clinical safety of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone: 12-lead ECG QTcF-interval	Up to Day 22	12-lead electrocardiogram (ECG) QTcF-interval for safety monitoring purpose. ECGs for safety purpose will be performed using the internationally recognized 12 leads with devices recorder after 10 min rest in supine position and before any blood draws. ECG will be recorded at a standard paper speed of 25 mm/s and gain of 10 mm/mV. Print-outs for each ECG will include: date, time, initials of the Investigator or its deputy.; The ECGs will be performed in 6 × 2 leads during this study. The corresponding source data will consist of the ECG recorder paper print-outs.; The ECGs will be read and analysed by the Investigator.
To evaluate the clinical safety of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone: 12-lead ECG PR Interval	Up to Day 22	12-lead electrocardiogram (ECG) PR Interval for safety monitoring purpose. ECGs for safety purpose will be performed using the internationally recognized 12 leads with devices recorder after 10 min rest in supine position and before any blood draws. ECG will be recorded at a standard paper speed of 25 mm/s and gain of 10 mm/mV. Print-outs for each ECG will include: date, time, initials of the Investigator or its deputy.; The ECGs will be performed in 6 × 2 leads during this study. The corresponding source data will consist of the ECG recorder paper print-outs.; The ECGs will be read and analysed by the Investigator.
To evaluate the laboratory safety, Hemoglobin, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, hemoglobin, from baseline to EoS visit.
To evaluate the laboratory safety, white blood cells count, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, white blood cells count, from baseline to EoS visit.
To evaluate the laboratory safety, mean corpuscular hemoglobin, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, mean corpuscular hemoglobin, from baseline to EoS visit.
To evaluate the laboratory safety, lymphocytes, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, lymphocytes, from baseline to EoS visit.
To evaluate the laboratory safety, eosinophils, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, eosinophils, from baseline to EoS visit.
To evaluate the laboratory safety, ALT, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, ALT, from baseline to EoS visit.
To evaluate the laboratory safety, creatinine, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, creatinine, from baseline to EoS visit.
To evaluate the laboratory safety, neutrophils, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, neutrophils, from baseline to EoS visit.
To evaluate the laboratory safety, GGT, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, GGT, from baseline to EoS visit.
To evaluate the laboratory safety, total bilirubin, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, total bilirubin, from baseline to EoS visit.
To evaluate the laboratory safety, total protein, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, total protein, from baseline to EoS visit.
To evaluate the laboratory safety, eGFR, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, eGFR, from baseline to EoS visit.
To evaluate the laboratory safety, calcium, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, calcium, from baseline to EoS visit.
To evaluate the Tmax of dextromethorphan's metabolite, dextrorphan (DXO), when co-administered with acoziborole.	Up to Day 22	DXO: tmax for Period 1 and Period 2.
To evaluate the laboratory safety, direct bilirubin, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, direct bilirubin, from baseline to EoS visit.
To evaluate the Tmax of dextromethorphan when co-administered with acoziborole.	Up to Day 22	Time to maximum observed plasma concentration (tmax) for dextromethorphan.
To evaluate the apparent terminal elimination half-life of midazolam when co-administered with acoziborole.	Up to Day 22	Apparent terminal elimination half-life (t½) for midazolam
To evaluate the AUC0-∞ of midazolam when co-administered with acoziborole.	Up to Day 22	AUC0-∞ for midazolam
To evaluate the AUC0-∞ of midazolam's metabolite, 1'hydroxy-midazolam, when co-administered with acoziborole.	Up to Day 22	1'-hydroxy-midazolam: AUC0-∞ for Period 1 and Period 2.
To evaluate the AUC0-24 of dextromethorphan's metabolite, dextrorphan (DXO), when co-administered with acoziborole.	Up to Day 22	DXO: AUC0-24 for Period 1 and Period 2.
To evaluate the AUC0-t of dextromethorphan's metabolite, dextrorphan (DXO), when co-administered with acoziborole.	Up to Day 22	DXO: AUC0-t for Period 1 and Period 2.
To evaluate the t½ of dextromethorphan's metabolite, dextrorphan (DXO), when co-administered with acoziborole.	Up to Day 22	DXO: t½ for Period 1 and Period 2.
To evaluate the AUC0-t of midazolam's metabolite, 1'hydroxy-midazolam, when co-administered with acoziborole.	Up to Day 22	1'-hydroxy-midazolam: AUC0-t for Period 1 and Period 2.
To evaluate the laboratory safety, bicarbonates, of acoziborole co-administered with midazolam and dextromethorphan as compared to administration of midazolam and dextromethorphan alone.	Up to Day 22	Laboratory safety assessments, bicarbonates, from baseline to EoS visit.
To evaluate the Acoziborole plasma concentrations when co-administered with midazolam and dextromethorpharm	Up to Day 22	Acoziborole plasma concentrations
To evaluate the AUC0-24 of midazolam's metabolite, 1'hydroxy-midazolam, when co-administered with acoziborole.	Up to Day 22	1'-hydroxy-midazolam:AUC0-24 for Period 1 and Period 2.
To evaluate the t½ of midazolam's metabolite, 1'hydroxy-midazolam, when co-administered with acoziborole.	Up to Day 22	1'-hydroxy-midazolam: t½ for Period 1 and Period 2.
To evaluate the Cmax of dextromethorphan's metabolite, dextrorphan (DXO), when co-administered with acoziborole.	Up to Day 22	DXO: Cmax for Period 1 and Period 2.
To evaluate the AUC0-∞ of dextromethorphan's metabolite, dextrorphan (DXO), when co-administered with acoziborole.	Up to Day 22	DXO: AUC0-∞ for Period 1 and Period 2.

Trial Locations

Locations (1)

Clinical Research Center (CRC) Ampang Hospital; 🇲🇾 Kuala Lumpur, Malaysia