None listed
Conditions
Interventions
Intervention1: Active: Participants will be administered ascending doses from low to high. In the SAD phase, a single morning dose will be administered on Day 1. In the MAD phase, doses will be admini
Sponsors
Dycine Pharmaceuticals Limited
VHypotenuse Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1.Adults -male or female, 18 to 55 years, determined as healthy by medical history, physical examination, vital signs, 12 lead ECG, and clinical laboratory tests. 2.BMI 18.0 to 32.0 kg per m squared inclusive and body weight greater than or equal to 50 kg at Screening. 3.Able to provide written informed consent, communicate with study staff, and comply with study procedures. 4.Females of non-childbearing potential NCBP are eligible - post-menopausal greater than or equal to 12 months, or surgically sterile: bilateral oophorectomy, hysterectomy, or bilateral tubal occlusion or ligation 5.Females of childbearing potential FCBP are eligible if they have negative pregnancy tests on the day of dosing and agree to use a highly effective contraception method failure rate less than 1 percent per year e.g, IUD, implant, combined hormonal contraception, or true abstinence from first study procedure through 30 days after last dose. 6.Male participants at screening must agree to practice adequate contraception and to avoid sperm donation from first study procedure through 30 days after last dose. 7.Able to swallow oral medications and tolerate fasting conditions as per protocol.
Exclusion criteria
Exclusion criteria: 1.Pregnant or breastfeeding females, or positive pregnancy test at Screening or Day -1 or Day 1. 2.Clinically significant disease: History or presence of any medical, psychiatric, or surgical condition that could affect safety, study participation, or data interpretation e.g, cardiovascular, hepatic, renal, respiratory, endocrine and neurological disorders. 3.Cardiac risk factors or abnormal ECG findings Baseline QTcF greater than 450 ms males or greater than 470 ms females, or a QTcF increase greater than 20 ms between Screening and Day -1, History of congenital long QT syndrome, torsades de pointes, syncope, heart failure, or clinically significant brady- or tachy- arrhythmia. 4.Laboratory abnormalities ALT or AST greater than 1.5 times ULN, total bilirubin greater than 1.2 times ULN unless Gilberts with normal direct bilirubin Alkaline phosphatase greater than 1.5 times ULN eGFR less than 60 mL per min per 1.73 m squared CKD EPI Creatine kinase CK greater than 1.5 times ULN or any evidence of active myopathy Clinically significant electrolyte abnormalities Potassium, Magnesium, Calcium not correctable before dosing Positive screening tests for HBsAg, HCV, or HIV 1 or 2 5.Acute illness or infection within 14 days before dosing e.g, fever, upper-respiratory or gastrointestinal infection. 6.Concomitant medication use a. Any prescription, over the counter, or complementary or alternative medicine within 14 days or 5 half-lives whichever longer before dosing, except protocol allowed rescue treatments. b. Potent CYP3A4 inhibitors or inducers or QT prolonging drugs e.g, azoles, macrolides, fluoroquinolones, and anti-arrhythmic drugs within 28 days before dosing. c. Consumption of grapefruit or Seville orange products within 7 days pre dose. 7.Musculoskeletal disorders Current or past tendonitis, arthropathy, myopathy, or inflammatory joint disease in the last 12 months that may confound marimastat related musculoskeletal safety assessment. 8.Gastrointestinal conditions affecting absorption e.g, significant malabsorption, major GI surgery and chronic diarrhoea. 9.Substance use a. Positive urine drug screen or breath alcohol test at admission pre dose. b. Positive Breath alcohol testing at admission pre dose. c. History of alcohol or substance use disorder within 12 months. d. Regular tobacco or nicotine use greater than 5 cigarettes per day or equivalent within the last 3 months or unwilling to abstain during confinement. 10.Participation in another interventional trial within 90 days or 5 half lives of the last investigational drug. 11.Blood donation or loss greater than 400 mL in previous 8 weeks, or plasma donation within 2 weeks prior to dosing. 12.Known hypersensitivity or intolerance to Nilotinib, Marimastat, Varespladib or Varespladib methyl, or any of the formulation excipients. 13.Any condition or finding which, in the investigators judgment, could jeopardise participant safety, interfere with protocol compliance, or confound PK or PD assessment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the safety and tolerability of single- and multiple-ascending doses of NMV as follows Incidence of Dose Limiting Toxicities and Number of serious adverse events and Number and severity of treatment emergent adverse eventsTimepoint: Dose Limiting Toxicity SAD - Day 1 to Day 3 MAD - Day 1 to Day 4. Safety Surveillance from Day 1 to Day 7 for SAD and Day 1 to Day 14 for MAD. SAEs and TEAE for SAD from Day 1 to Day 7 and MAD from Day 1 to Day 14 | — |
Secondary
| Measure | Time frame |
|---|---|
| To characterise the PK of each drug NMV given in combination following single and multiple ascending dosesTimepoint: SAD Day 1 serum at 0 hours to 48 hours and MAD Day 1 0 hours to 120 hours and Day 7 0 hours to 48 hours tail sample; To characterise the PK of each drug NMV given in combination following single and multiple ascending doses To assess potential drug drug interactions DDIs between NMV through comparative PK evaluationTimepoint: SAD Day 1 serum at 0 hours to 48 hours and MAD Day 1 0 hours to 120 hours and Day 7 0 hours to 48 hours tail sample;To evaluate dose proportionality and accumulation ratios of each drug across different dose levelsTimepoint: SAD Day 1 serum at 0 hours to 48 hours and MAD Day 1 0 hours to 120 hours and Day 7 0 hours to 48 hours tail sample | — |
Countries
India
Contacts
Public ContactTallapally Vinay
Dycine Pharmaceuticals Ltd
Outcome results
None listed