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PBL 1427 is a Dipeptidyl peptidase (DPP)-IV inhibitor being developed for treatment of type 2 diabetes. Although a number of DPP-IV inhibitors have been described, there still exists a need for new DPP-IV inhibitors that have better half-life, advantageous potency, stability and selectivity, less toxicity and/or better pharmacodynamic properties.
As per the randomization schedule, capsule(s) of A or B will be administered to each subject with 240 mL of water at ambient temperature. Subjects will be instructed not to chew or crush the capsule(s) but to consume it as a whole. Compliance for dosing will be assessed by a thorough check of the oral cavity immediately after dosing. Administration of investigational products will be carried out while the subjects are in sitting posture and they will be instructed to remain seated for two hours after dosing except when clinically indicated to change the posture or in case of any natural exigency. Thereafter, the subjects will be allowed to engage in normal activities while avoiding severe physical exertion.
The following treatments in the below cohorts will be followed as given below:
Cohort 1: A single oral dose of 20 mg of PBL 1427 (n=6) or placebo (n=2) Cohort 2: A single oral dose of 40 mg (20 mg X 2 capsules) of PBL 1427 (n=6) or placebo (n=2) Cohort 3: A single oral dose of 80 mg (20 mg X 4 capsules) of PBL 1427 (n=6) or placebo (n=2) Cohort 4: A single oral dose of 150 mg of PBL 1427 (n=6) or placebo (n=2) Cohort 5: A single oral dose of 300 mg (150 mg X 2 capsules) of PBL 1427 (n=6) or placebo (n=2) Cohort 6: A single oral dose of 600 mg (150 mg X 4 capsules) of PBL 1427 (n=6) or placebo (n=2)
Dose levels may be modified and intermediate dose levels might be tested to determine the maximum tolerated dose (MTD)
The number of cohorts, dose levels, frequency and conditions of administration for the subsequent cohort may be altered by the Principal investigator and Sponsor after evaluation of the results of the previous group.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PBL 1427 capsules | Experimental |
| |
| Matching placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Matching placebo | Drug | Matching Placebo, single dose |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of subjects with adverse events | Safety and tolerability of PBL 1427 will be assessed after single ascending doses when administered alone on the basis of AEs, vital signs (BP, pulse rate, and body temperature), ECG, laboratory parameters and clinical assessment. | Pre-dose and upto Day 5-9 |
| Pharmacokinetics Variables (Cmax, tmax, AUC, t1/2, kel, CL/F & Vz/F) | Pharmacokinetic parameters of single ascending doses of PBL 1427 : For each subject, blood will be collected at the following time points: pre-dose, 0.25, 0.50, 0.75 1, 1.5, 2, 3, 4, 6, 8, 10, 14, 16, 20, 24, 36 and 48 h post-dose. | 48 hrs post dose |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacodynamics assessment (glucose, insulin, C-peptide, lactic acid) | Pharmacodynamics will be assessed using markers like glucose, insulin, C-peptide, lactic acid and the exploratory markers plasma DPP-IV activity and plasma GLP-1 (Glucagon-like peptide I) levels | Pre-dose and upto 4 h post-dose |
| Exploratory markers (plasma DPP-IV activity and GLP-1 levels) |
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Inclusion Criteria: Subjects to be enrolled in this trial must fulfil all of these criteria:
Exclusion Criteria: Subjects meeting any of these criteria will not be enrolled in the study:
Note: In case the blood loss is ≤ 200 mL; subject may be dosed 60 days after blood donation or last sample of the previous study
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Dr Deepak C Chilkoti | Contact | +91-129-4090 900 | Deepak.chilkoti@fortis-cro.com |
| Name | Affiliation | Role |
|---|---|---|
| Dr Deepak C Chilkoti | Head-Clinical Operations | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fortis Clinical Research Ltd | Recruiting | Faridabad | Haryana | 121 002 | India |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| PBL 1427 capsules |
| Drug |
PBL 1427 capsules 20 mg and 150 mg, single dose |
|
Pharmacodynamics will be assessed using markers like glucose, insulin, C-peptide, lactic acid and the exploratory markers plasma DPP-IV activity and plasma GLP-1 (Glucagon-like peptide I) levels |
| Pre-dose and upto 48 h after dosing |