This First in Human (FIH) Phase I study intends to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ZYDPLA1 in normal healthy adult volunteers.
Glucose-dependent insulinotropic polypeptide (GIP) and Glucagon-like peptide (GLP-1) are incretin hormones, which stimulate glucose dependent insulin secretion, inhibit glucagon secretion, delay gastric emptying, suppress appetite and improve peripheral glucose uptake and disposal. Dipeptidyl peptidase-IV (DPP-IV) is a serine protease, which selectively cleaves the first two amino acids of GIP and GLP-1 thereby making it inactive. Inhibition of DPP-IV activity elevates endogenous GIP, GLP-1 and insulin levels thereby improving glucose excursion and exhibits antidiabetic activity. Since no orally active GLP-1 agonists are available, clinically orally bioavailable DPP-IV inhibitors hold great potential for the treatment of type 2 diabetes mellitus. Cadila Healthcare Ltd. developed a novel and orally bioavailable DPP-IV inhibitor (ZYDPLA1). In-vitro studies confirm selective DPPIV inhibitory activity of the ZYDPLA1. Pre-clinical in vivo pharmacodynamic, absorption, distribution, metabolism and excretion (ADME) \& toxicological studies showed the promising antidiabetic activity, good exposure and safety profile of ZYDPLA1(in various animal models). Hence a randomized, double-blind, placebo-controlled first in man trial proposed to evaluate the safety and tolerability of ZYDPLA1 in healthy volunteers. This study included 4 plans: i) single dose escalation study ii) multiple dose escalation study, iii) gender effect study and iv) food effect study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
QUADRUPLE
Enrollment
84
The oral dose of ZYDPLA1 tablet administered with 240 ± 10 mL of water at ambient temperature.
The oral dose of placebo tablet administered with 240 ± 10 mL of water at ambient temperature.
Profil Institute for Clinical Research
Chula Vista, California, United States
Safety and tolerability assessed by monitoring adverse events, clinical, laboratory, electrocardiogram, and vital signs examinations.
Time frame: 14 Days (Plan 1, III, and IV);
Safety and tolerability assessed by monitoring adverse events, clinical, laboratory, electrocardiogram, and vital signs examinations.
Time frame: 28 Days (Plan II)
Pharmacokinetic assessment: Maximum plasma concentration (Cmax)
Time frame: 14 Days (Plan I, III, and IV)
Maximum plasma concentration (Cmax)
Time frame: 28 Days (Plan II)
Time to reach maximum plasma concentration (Tmax)
Time frame: 14 Days (Plan I, III, and IV)
Time to reach maximum plasma concentration (Tmax)
Time frame: 28 Days (Plan II)
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)
Time frame: 14 Days (Plan I, III, and IV)
Area under the curve from the time of dosing to the last measurable concentration (AUC0-t)
Time frame: 28 Days (Plan II)
Area under the curve from the time of dosing to the infinity (AUC 0-inf)
Time frame: 14 Days (Plan I, III, and IV)
Area under the curve from the time of dosing to the infinity (AUC 0-inf)
Time frame: 28 Days (Plan II)
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Terminal half life (t1/2)
Time frame: 14 Days (Plan I, III, and IV)
Terminal half life (t1/2)
Time frame: 28 Days (Plan II)
Elimination rate constant (λz)
Time frame: 14 Days (Plan I, III, and IV)
Elimination rate constant (λz)
Time frame: 28 Days (Plan II)
Clearance (CL)
Time frame: 14 Days (Plan I, III, and IV)
Clearance (CL)
Time frame: 28 Days (Plan II)
Volume of distribution (Vd)
Time frame: 14 Days (Plan I, III, and IV)
Volume of distribution (Vd)
Time frame: 28 Days (Plan II)
Accumulation index
Time frame: 28 Days (Plan II)
Pharmacodynamic effect (Plan I, III, and IV) assessment by monitoring primary parameters: Plasma DPPIV
Time frame: 14 Days
Pharmacodynamic effect (Plan II) assessment by monitoring primary parameters: Plasma DPPIV
Time frame: 28 Days
Glucagon-like peptide-1 (active and total)
Time frame: 14 Days
Glucagon-like peptide-1 (active and total)
Time frame: 28 Days
Secondary parameters: Plasma glucose
Time frame: 14 Days
Plasma glucose
Time frame: 28 Days
Serum insulin
Time frame: 14 Days
Serum insulin
Time frame: 28 Days
C-peptide
Time frame: 14 Days
C-peptide
Time frame: 28 Days
Glucagon
Time frame: 14 Days
Glucagon
Time frame: 28 Days