None listed
Conditions
Interventions
Intervention1: ISC 17536 NCG 11.5mg SLS: New core granules with 11.5mg SLS: Dose: 60mg, 90mg, and 250mg
Dosage Form: Capsule
Dosage Frequency: One single dose
Route of Administration: Oral
Intervention2: ISC 17536 NCG mix: New core granules plus EC6 granules: Dose: 90mg
Route of Administration: Oral
Intervention3: ISC 17536 NCG 20mg SLS: New core granules with 20mg SLS: Dose: 160mg and 320mg
Route of Administration: Oral
Intervention4: EC6: ISC 17536 Enteric Coated formulations of new core granules, pH6: Dose: 30mg
Route of Administration: Oral
Control Intervention1: ISC 17536 Core Granules for suspension (CG): Dose: 90mg, 160mg, and 250mg
Dosage Form: Suspension
Sponsors
Glenmark Pharmaceuticals Ltd
ICHNOS SCIENCES SA
Eligibility
Inclusion criteria
Inclusion criteria: 1. Normal healthy male of 18 to 45 years of age (both inclusive) at the time of initial written informed consent. 2. Body mass index (BMI) >= 18.5 kg/m2 and =50 kg at screening. 3. Provide written informed consent prior to any protocol-related procedures, including screening evaluations. Subject must be able to understand the consent form and instructions and to provide consent directly; no guardian or caregiver may provide consent for the subject. 4. Negative for drugs of abuse at check-in. 5. Negative for alcohol consumption at check-in. 6. Able and willing to abstain from methylxanthine-containing beverages or food (coffee, tea, chocolate, caffeinated sodas, cola or â??power drinksâ??) from 48h prior to admission on D-1 and throughout the study through the final end-of-study visit (on D25). 7. Able and willing to abstain from grapefruit juice from 7 days prior to admission on D-1 and throughout the study duration, through D25. 8. Non-smokers and those who have not consumed tobacco or tobacco products at least for last 12 months and willing to abstain from smoking and the use of other tobacco-containing or nicotine-containing products (including but not limited to cigarettes, hookah, vaping, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) or use of any electronic cigarette for vaping (including with non-nicotine containing chemicals) throughout the study until D25. 9. Negative urine cotinine test at screening and at admission to CRU. 10. Men of child bearing potential must agree to protocol-specified contraception requirements.
Exclusion criteria
Exclusion criteria: 1. Has clinically significant results on physical examination, medical history, 12-lead ECG, chest X-ray, or lab investigations that would increase risk to the subject by participating in the study, as determined by the Investigator. 2. History of relevant drug allergies, food allergies or known allergy to ISC 17536 or its excipients, as determined by the Investigator. 3. History of clinically significant (as determined by the Investigator) hematologic, renal, endocrine, pulmonary, GI (presence of active peptic ulcer disease, GI bleeding, chronic gastritis, gastric bypass surgery, inflammatory bowel disease or chronic diarrhea), cardiovascular, hepatic, psychiatric, neurologic (including any active seizure disorder requiring therapy with antiepileptic drugs, head injury or untreated convulsion), or allergic disease (including drug allergies, but excluding untreated, mild seasonal allergies). 4. Clinically significant alcohol or drug abuse/addiction as determined by the Investigator. 5. Positive Hepatitis B Virus Surface Antigen (HBsAg) or Hepatitis B antibody to core protein, Hepatitis C Virus Antibody (HCV Ab) or antibodies to the human immunodeficiency virus (HIV-1/2 Antibody [HIV-1/2 Ab]). 6. History of liver disease or any abnormal liver function tests at screening [Alanine Aminotransferase (ALT)/ Aspartate Aminotransferase (AST)/Alkaline Phosphatase (ALP)/Bilirubin (BILI)) >1.5x upper limit of normal (ULN)]. 7. Clinically significant ECG abnormalities at screening including: - An abnormal PR interval considered by the investigator as clinically significant (>= 220 msec or - QTc prolongation (QTcF >= 450 msec), OR - Sinus bradycardia ( - Any history of myocardial ischemia/infarction (either changes suggesting acute ischemia/infarction or changes from previous tracings compatible with the infarction), OR - Heart rate 100 bpm that is considered clinically significant by the investigator. 8. Supine systolic blood pressure (SYSBP) >=140 mm Hg or =90 mm Hg or 9. Has acute GI symptoms at the time of screening or at admission to CRU (eg. nausea, vomiting, diarrhea, heartburn). 10. Received any investigational drug in any clinical study within 3 months or less than 5 half-lives prior to screening, or are on extended follow-up from such a clinical study. 11. Previous randomization in any ISC 17536 study. 12. Received moderate or strong inhibitors or inducers of CYP3A4 enzymes during the 30 days or 5 half-lives prior to screening, whichever is longer (including but not limited to the drugs listed in excluded medication). 13. Received herbal/Ayurveda medication/supplements, St Johnâ??s wort, or any food or drink containing grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family (eg, cauliflower, cabbage and cruciferous vegetables; kale, broccoli, watercress, collard greens, kohlrabi, brussel sprouts, mustard) or charbroiled meat within 24 hours prior to admission (Day -1). 14. Has taken any medications, including over-the-counter (OTC) medications, within 14 days before study drug adm
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Systemic exposure of ISC 17536 characterized by maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC0-24, AUC0-72, AUC0-last and AUC0-inf) of ISC 17536 following the administration of CG, NCG 11.5 mg SLS, NCG Mix, NCG 5 mg SLS and EC6Timepoint: 24hours post-dose, 72hours post-dose, and 576 hrs (time to last detectable level in plasma); time to maximum plasma concentration | — |
Secondary
| Measure | Time frame |
|---|---|
| Additional plasma PK parameters of ISC 17536 including time to reach Cmax (tmax), apparent terminal elimination rate constant (λz) and terminal elimination half-life (t½) with all formulationsTimepoint: time to maximum plasma concentration and other parameters will be calculated;Assessed by incidence of adverse events (AEs), clinical laboratory tests, vital signs (including orthostatic measures), electrocardiograms (ECGs), and physical examination.Timepoint: Initiation to End of Study;Mean estimate of slope from the power model (linear regression with log-transformed Cmax and AUC parameters to the log-transformed dose) for dose proportionality of ISC 17536 with NCG 11.5 mg SLS.Timepoint: dose proportionality using power model with Cmax and AUC for entire duration of assessment;Metabolite/Parent Percentage for GRC 18106 [M1], GRC 18143 [M2], and GRC 18129 [M6] versus ISC 17536 (M/P [%]).Timepoint: entire duration of study assessment;Plasma PK parameters (Cmax, tmax, AUC0-last, AUC0-inf, λz, and t½) of ISC 17536 metabolites (GRC 18106, GRC 18143, and GRC 18129).Timepoint: maximum plasma concentration, time to maximum plasma concentration, plasma concentration-time curve from time zero up to infinity, time zero to the last quantifiable concentration, and other derived parameters. | — |
Countries
India
Contacts
Public ContactVikas Joshi
Glenmark Pharmaceuticals Ltd
Outcome results
None listed