Healthy Adult Participants
Conditions
Keywords
Drug-drug interaction study, Pharmacokinetics, Healthy adults, Fosmanogepix, Manogepix
Brief summary
This is a Phase 1, fixed-sequence, multiple-dose study in approximately 42 healthy adult participants. The study will be conducted in two parts. Part 1 will evaluate the effect of fosmanogepix, through exposure to its active moiety manogepix, on selected CYP enzymes and on the concentration-QT interval corrected for heart rate (QTc). Part 2 will evaluate the effect of manogepix on CYP2C8 and on selected drug transporters. The maximum study duration will be approximately 13.5 weeks for participants in Part 1 and approximately 12 weeks for participants in Part 2.
Interventions
DRUGFosmanogepix
Fosmanogepix will be administered as an intravenous infusion or as an oral tablet
OTHERPlacebo
Placebo will be administered as an intravenous infusion or as an oral tablet
OTHERThe medicine cocktail (caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan and midazolam)
The medicine cocktail will be administered as tablet, capsule, or drink to be swallowed
OTHERProbe substrates (repaglinide, rosuvastatin, and digoxin)
Probe substrates will be administered as oral tablets
Sponsors
Basilea Pharmaceutica
Biomedical Advanced Research and Development Authority
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index of 18 to 30 kg/m2, inclusive, and a total body weight \> 50 kg at screening * Healthy, as determined by medical history, physical examination, and other procedures, including blood pressure and pulse rate, 12-lead ECG, clinical laboratory tests (hematology, clinical chemistry, coagulation, urinalysis), and an estimated glomerular filtration rate (eGFR) ≥ 80 mL/min/1.73m2 (CKD-EPI formula), at Screening and Day -2. * Women of childbearing potential must agree to use highly effective forms of contraception during treatment and observation.
Exclusion criteria
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease. * Active infection. * Any condition possibly affecting drug absorption. * History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, HBcAb, HCVAb, and syphilis * Subjects who are pregnant, breastfeeding, or plan to become pregnant during the study. Medical history of neurological disorders, including abnormal movements or seizures. * Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior, or laboratory abnormality that may increase the risk of study participation or, in the Investigator's judgment, make the subject inappropriate for the study. * History of allergy or hypersensitivity or other contraindication to any of the drugs to be administered, or to one of the components of the study drugs, as determined by the Investigator. * History of risk factors for QT prolongation, Torsades de Pointes, or uncorrected hypokalemia/hypomagnesemia. * Previous administration of an investigational drug (including a vaccine) within 60 days or five half-lives (whichever is longer) prior to the first study drug administration on Day 1. * For Part 1 only, poor metabolizers of CYP2D6 (\*4/\*4; \*4/\*5; \*5/\*5), CYP2C9 (\*2/\*2; \*2/\*3; \*3/\*3), and/or CYP2C19 (\*2/\*2) (determined at Screening or from available historical data). * Supine systolic blood pressure (SBP) \> 140 mmHg or diastolic blood pressure (DBP) \> 90 mmHg, and pulse rate \> 100 beats per minute (bpm) or \< 40 bpm Supine 12-lead ECG demonstrating any of the following clinically-relevant abnormalities that may affect subject safety or interpretation of the study results: QTcF interval \> 450 msec, QRS interval \> 120 msec, complete left bundle branch block, signs of an acute or indeterminate-age myocardial infarction, ST T interval changes suggestive of myocardial ischemia, second- or third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias * Subjects with AST or ALT \> 1.0 × ULN. * Blood (excluding plasma) donation or blood loss \> 500 mL within 60 days prior to Screening. * History of alcohol abuse or binge drinking and/or any other illicit drug abuse or dependence. * Use of tobacco or nicotine-containing products or devices within 3 months of Screening. * Caffeine consumption ≥ 800 mg per day at Screening. * Use of prescription/non-prescription (including vaccines) drugs or dietary/herbal supplements within 21 days (or five half-lives, whichever is longer) prior to Day -2, except for hormonal contraceptives, or paracetamol up to 1,500 mg/day.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Maximum Plasma Concentration (Cmax) of the medicine cocktail when administered alone or in combination with manogepix at steady state | At Day 1 and Day 22 | The effect of fosmanogepix will be checked by comparing the blood levels of the medicine cocktail when taken alone or after administration of fosmanogepix. |
| Part 1: Area under the concentration-time curve (AUC) of the medicine cocktail when administered alone or in combination with manogepix at steady state | At Day 1 and Day 22 | The effect of fosmanogepix will be checked by comparing the blood levels of the medicine cocktail when taken alone or after administration of fosmanogepix. |
| Part 2: Maximum Plasma Concentration (Cmax) of probe substrate cocktail when administered alone or in combination with manogepix at steady state | From Day 1 to Day 20 | The effect of fosmanogepix will be checked by comparing the blood levels of probe substrate cocktail when taken alone or after administration of fosmanogepix. |
| Part 2: Area under the concentration-time curve (AUC) of probe substrate cocktail when administered alone or in combination with manogepix at steady state | From Day 1 to Day 20 | The effect of fosmanogepix will be checked by comparing the blood levels of of probe substrate cocktail when taken alone or after administration of fosmanogepix. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Placebo-corrected change from baseline in the heart-rate corrected QT interval using Fridericia's formula | From Day 5 to Day 12 | Electrocardiogram (ECG) monitoring will be performed during placebo and fosmanogepix administration. |
| Number of participants reporting treatment emergent adverse events (TEAEs) | From screening to week 13.5 | To evaluate the safety and tolerability of fosmanogepix when administered in combination with the medicine cocktail or probe substrates cocktail |
Countries
Netherlands
Contacts
CONTACTThomas Kaindl, MD
STUDY_DIRECTORThomas Kaindl, MD
Basilea Pharmaceutica International Ltd, Allschwil
Outcome results
None listed