A Randomized, Double Blind Placebo Controlled Phase 1 Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ZYGK1, a Novel Glucokinase Activator, Following Oral Administration in Healthy Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Suspended
- Sponsor
- Zydus Lifesciences Limited
- Enrollment
- 96
- Locations
- 1
- Primary Endpoint
- Safety and tolerability
Study Overview
Brief Summary
The purpose of this study is to determine (1) whether ZYGK1 is safe and well tolerated, (2) the pharmacokinetics (what body does to ZYGK1) and (3) pharmacodynamics (what drugs does to the body) in the healthy and diabetic subject.
Detailed Description
This study will be a randomized, double blind, placebo controlled study and is divided into four plans:
- Plan I: Single Ascending Dose (SAD) Study
- Plan II: Multiple Ascending Dose (MAD)Study
- Plan III: Gender Effect study
- Plan IV: Food Effect study
First Plan I, Plan III and Plan IV will be conducted in healthy volunteers. After reviewing the results, decision shall be taken whether the multiple ascending doses shall be studied in healthy human volunteers or in subjects with type 2 diabetes.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age: 18-45 years
- •Mentally, physically, and legally eligible to give informed consent
- •Male and female volunteers weighing between 50-75 kg and 45-75 kg (4) respectively.
- •Ability to communicate effectively with the study personnel
- •Willingness to adhere to the protocol requirements
- •For gender effect study, only females with history of sterility or at least one year menopause or use of long acting nonhormonal contraceptive measures (e.g., intrauterine device) will be recruited.
- •At least one panel, in single ascending dose and multiple ascending dose will include subjects with type 2 diabetes as defined by American Diabetes Association
Exclusion Criteria
- •Presence or history of hypersensitivity to any of the active or inactive ingredients of ZYGK1 formulation
- •Presence or history of pancreatitis at any time (Serum Amylase/Serum Lipase more than upper normal limit (UNL))
- •Presence or history of severe gastrointestinal disease in the last 6 months
- •Presence or history of renal insufficiency at any time (serum creatinine >UNL)
- •Active liver disease and/or liver transaminases greater than 1.5 X UNL
- •History or presence of other systemic disorders or diseases (e.g., respiratory, gastrointestinal, endocrine, immunological, dermatological, neurological, psychiatric disease or any other body system involvement)
- •Abnormal bleeding time (BT), clotting time (CT), prothrombin time (PT), and activated partial prothrombin time (APTT)
- •History or presence of any medication in the last 14 days
- •History or presence of significant alcoholism or drug abuse within the past 1 year
- •History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco products (more than 10 times per day)
- •Difficulty with donating blood
- •Systolic blood pressure more than 140 mmHg and less than 100 mmHg and diastolic blood pressure more than 90 mmHg and less than 60 mmHg
- •Pulse rate less than 60 minute and more than 100/minute
- •Any clinically significant laboratory findings during screening
- •History or presence of any clinically significant electrocardiogram (ECG) abnormalities during screening
- •Major illness and/or major surgery in last 3 months
- •Volunteers who have participated in any drug research study other than the present trial within past 3 months
- •Volunteers who have donated one unit (350 ml) of blood in the past 3 months
Arms & Interventions
Placebo
Placebo tablets
Intervention: Placebo (Drug)
ZYGK1
ZYGK1 tablets; 0.125, 0.25, 0.5, 1, 2, ... mg.
Dose escalation will continue till single AE occurs in any block of 3 volunteers on ZYGK1 or pharmacokinetic (dose linearity) saturation is reached or desired PK/PD effect is achieved
Intervention: ZYGK1 (Drug)
Outcomes
Primary Outcomes
Safety and tolerability
Time Frame: Upto 14 Days
Safety and tolerability for- * Plan I, Plan III and Plan IV \[Time frame: up to Day 8\] * Plan II \[Time frame: upto Day 14\] Frequency of adverse events will be assessed at each dose level.
Secondary Outcomes
- Pharmacokinetics(7 Days)
- Pharmacodynamics(7 Days)