Leriglitazone for Adrenoleukodystrophy

Inclusion criteria

• {"criterion_text":"- Healthy male participants (aged 18 to 50 years [inclusive]) with a BMI between 18 and 30 kg/m2 (inclusive).\n- Male participants who are voluntarily able to give informed consent.\n- Non-sterilized male participants with female partners of childbearing potential are eligible to participate if they agree to ONE of the following from Screening (signing the Informed Consent Form [ICF]) until at least 90 days after the last dose of study intervention. A) Are abstinent from penile-vaginal intercourse. B) Agree to use a male condom and have their partner use a contraceptive method with a failure rate of < 1% per year when having penile-vaginal intercourse with a woman of childbearing potential who is not currently pregnant (see Section 10.4). In addition, male participants must refrain from donating sperm from Screening (signing the ICF) until at least 12 weeks after the last dose of study intervention. The ICF will include information regarding potential effects on human spermatogenesis.\n- Participants without any clinically significant finding upon completion of medical history, physical examination, and clinical laboratory test results, in the opinion of an Investigator.\n- Ability and willingness to abstain from alcohol, caffeine, and methylxanthine containing beverages or food (eg, coffee, tea, cola, chocolate, energy drinks) from 72 hours (3 days) prior to admission to the clinical research center and during the stay in the clinical research center."}

Exclusion criteria

• {"criterion_text":"- All female participants will be excluded.\n- Participants with any history or presence of suicidal ideation.\n- Participants with any history or presence of malignancy.\n- Participants who have a history or presence of sleep apnea.\n- Participants who have a clinically significant relevant surgical history within 3 months prior to screening. a) Participants with a history of bariatric surgery at any time are to be excluded.\n- Participants who have a clinically significant relevant family history of diseases of genetic origin.\n- Participants who have a history or presence of relevant atopy including any confirmed significant allergic reactions against any drug, or multiple drug allergies (non-active hay fever is acceptable), history of anaphylaxis, any foods allergies.\n- Participants who have a history or presence of any other hypersensitivity reaction in general which may affect their safety in this study, including contact hypersensitivity to ECG electrodes.\n- Participants who: a) Have any history of alcoholism and/or drug abuse. b) Have any known factor, condition, or disease that might interfere with treatment compliance, study conduct, or interpretation of the results such as drug or alcohol dependence or psychiatric disease. c) Test positive for alcohol or drugs of abuse at screening and/or on each admission. d) Consume more than 14 units of alcohol a week. 1 unit of alcohol is equivalent to 8 g of pure alcohol (unit = 1 glass of wine [125 mL] = 1 measure of spirits = ½ pint of beer).\n- Participants who smoke regularly or have smoked cigarettes (or equivalent) and/or regularly use nicotine-based products within 6 months prior to first admission.\n- Participants who demonstrate excess in xanthine (eg, coffee, tea, cola drinks, and chocolate) consumption (more than 8 cups of coffee or equivalent per day).\n- Participants of East Asian ancestry will be excluded from Part C to reduce the risk of severe AEs by carbamazepine (observed in those carrying HLA3101 or HLA-B1502).\n- Participants who have a clinically significant infection or known inflammatory process at screening or at admission on Day −1.\n- Participants who have acute gastrointestinal symptoms at the time of screening or admission on Day −1 (eg, nausea, vomiting, diarrhea, or heartburn).\n- Participants who have a chronic or acute infection (viral, bacterial, or other) at the time of screening or admission on Day −1.\n- Participants with clinically significant laboratory safety test results at screening and/or on admission on Day −1, and in particular: a) Liver function tests outside 1.5 × ULN of the local reference range. b) Renal function tests outside of the ULN of the local reference range. c) Absolute neutrophile count outside of the local reference range. d) Hemoglobin level < 12 g/dL.\n- Participants who have a positive test result for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, or human immunodeficiency virus (I and II) antibody.\n- Participants with an infection requiring antibiotic therapy within the last 1 month prior to screening.\n- Participants who have received a live vaccine within 6 months prior to screening in this study or during the study.\n- Participants who have received any other vaccine within 21 days prior to screening of this study or during the study.\n- Participants whose screening supine BP ≥ 140 mmHg (systolic) or ≥ 90 mmHg (diastolic), following at least 5 minutes of supine rest. If BP is ≥ 140 mmHg (systolic) or ≥ 90 mmHg (diastolic), the BP should be repeated 2 more times and, if within limits, the participant can be enrolled\n- Participants whose screening supine 12-lead ECG demonstrates a QTcF interval > 450 msec or a QRS interval > 120 msec. If the QTcF exceeds 450 msec, or the QRS exceeds 120 msec, the ECG should be repeated 2 more times and, if within limits, the participant can be enrolled\n- Males with female partners who are pregnant, lactating, or planning to attempt to become pregnant during the study or within 90 days after dosing of the study intervention.\n- Participants who have used any prescribed medications within 30 days of admission, or less than 5 half-lives (whichever is longer).\n- Participants who have used over the counter medication (excluding routine vitamins, sporadic acetaminophen, but including megadose vitamin therapy [intake of 20 to 600 times the recommended daily dose], herbal, and dietary supplements) within 7 days of admission.\n- Participants who have received strong inhibitors or inducers of CYP enzymes including natural products within 30 days of admission or within 5 half-lives of such drugs, whichever is the longest. See list of inhibitors/inducers at https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers.\n- Participants who have received the last dose of an investigational product more than 3 months ago but who are on extended follow-up.\n- Participants who have previously received leriglitazone in another study.\n- Participants who have lost or donated > 500 mL of blood within 90 days prior to screening or intend to donate blood or blood products during the study.\n- Participants who have consumed grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, Seville orange juice, or other products containing grapefruit or Seville oranges from 7 days prior to admission to the clinical research unit.\n- Participants who are affiliated with the Sponsor, contract research organization, or clinical research center.\n- Participants who are considered to be consenting under duress.\n- Participants with dietary restrictions such as medical restrictions or those on a vegan diet.\n- Participants who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematologic, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, and connective tissue diseases or disorders.\n- Participants who, in the opinion of an Investigator (or designee), should not participate in this study.\n- Known type 1 or 2 diabetic.\n- Participants who have a history or presence of relevant drug hypersensitivity or intolerance to pioglitazone, any other thiazolidinedione, leriglitazone, gemfibrozil, carbamazepine, and itraconazole.\n- Participant is taking or has taken honokiol, pioglitazone, or other tiazolidinediones within 3 months prior to screening.\n- Participant has a requirement for treatment with a prohibited concomitant medication.\n- Participant has a condition that could modify the absorption of the study intervention."}

Primary endpoints

• {"endpoint_text":"- To determine the DDI effect on the single-dose PK of oral leriglitazone as substrate when coadministered with gemfibrozil (Part A), itraconazole (Part B), or carbamazepine (Part C) as precipitants. Primary endpoint: Leriglitazone – Cmax, AUC(0-last), AUC(0-inf).","definition_or_measurement_approach":"PK parameters measured for leriglitazone: Cmax, AUC(0-last), AUC(0-inf) following single dose when coadministered with specified precipitants (Parts A-C)."}
• {"endpoint_text":"- To determine the effect of food (highfat breakfast) on the single-dose PK of oral leriglitazone (Part D). Primary endpoint: Leriglitazone – Cmax, AUC(0-last), AUC(0-inf)","definition_or_measurement_approach":"PK parameters measured for leriglitazone: Cmax, AUC(0-last), AUC(0-inf) comparing fed (high-fat breakfast) versus fasted conditions (Part D)."}

Secondary endpoints

• {"endpoint_text":"- To determine the DDI effect on the single-dose PK of oral leriglitazone as substrate when coadministered with gemfibrozil (Part A), itraconazole (Part B), or carbamazepine (Part C) as precipitants. Secondary endpoints: a) Leriglitazone – tmax, λz, t1/2, CL/F, and Vz/F. b) M3 – Cmax, tmax, AUC(0-inf), λz, and t1/2. c) Metabolite/parent (MR) ratios [ie, MRCmax, MRAUC(0last), and MRAUC(0inf)].","definition_or_measurement_approach":"Secondary PK parameters for leriglitazone (tmax, λz, t1/2, CL/F, Vz/F), metabolite M3 PK (Cmax, tmax, AUC(0-inf), λz, t1/2), and metabolite/parent ratio metrics (MRCmax, MRAUC(0last), MRAUC(0inf)) measured in Parts A-C."}
• {"endpoint_text":"- To determine the effect of food (highfat breakfast) on the single-dose PK of oral leriglitazone (Part D). Secondary endpoint: a)Leriglitazone – tmax, λz, t1/2, CL/F, and Vz/F. b) M3 – Cmax, tmax, AUC(0-inf), λz, and t1/2. c) Metabolite/parent (MR) ratios [ie, MRCmax, MRAUC(0last), and MRAUC(0inf)].","definition_or_measurement_approach":"Secondary PK parameters measured for leriglitazone and M3 and metabolite/parent ratios in fed (high-fat breakfast) versus fasted comparisons (Part D)."}
• {"endpoint_text":"- Reported AEs, and changes in electrocardiograms (PR, QRS, QT, and QTcF), vital signs, and clinical safety laboratory tests.","definition_or_measurement_approach":"Safety endpoints: incidence and severity of adverse events, ECG interval changes (PR, QRS, QT, QTcF), vital signs, and laboratory safety tests collected and reported per study schedule."}
• {"endpoint_text":"- Parts A, B, and C: To explore the potential impact of CYP2C8 and CYP3A4 gene polymorphisms on the PK of leriglitazone. Endpoint: Serum gene expression levels of CYP2C8 and CYP3A4 polymorphism versus PK.","definition_or_measurement_approach":"Exploratory pharmacogenetic analysis comparing serum gene expression / polymorphism status of CYP2C8 and CYP3A4 with leriglitazone PK parameters."}
• {"endpoint_text":"- Part B: To explore the potential impact of CYP3A5 gene polymorphism on the PK of leriglitazone when given concomitantly with CYP3A4 inhibitors (eg, itraconazole). Endpoint: Serum gene expression levels of CYP3A5 polymorphism versus PK.","definition_or_measurement_approach":"Exploratory analysis of CYP3A5 polymorphism (serum gene expression levels) in relation to leriglitazone PK when coadministered with CYP3A4 inhibitors."}

Poland

Earliest CTIS Part Ii Submission Date

23-07-2025

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

281

Number Of Sites

1

Number Of Participants

73

Primary sponsor

Full Name

Minoryx Therapeutics S.L.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain