A dose range finding study of novel oral insulin (IN-105) under fed conditions in type 2 diabetes mellitus subjects.
OBJECTIVE
The objective of the study was to establish the dose response of IN-105 tablets and explore a possible therapeutic window in type 2 diabetes subjects poorly controlled on metformin.


METHODS
The primary objective was to examine the effect of sequential single ascending doses of IN-105 on the plasma glucose concentration under fed conditions. All subjects received, sequentially, matching placebo, 10, 15, 20 and 30 mg IN-105 tablets in five consecutive periods. Tablets were administered 20 min prior to meal in all the periods. Plasma levels of immunoreactive insulin, C-peptide and glucose were measured up to 180 min from the time of dosing. The changes in postprandial glucose levels at 120 min in response to IN-105 administration were also compared against those of placebo.


RESULTS
Changes in glucose from baseline (mean +/- s.d.) at 140 min (2 h postprandial) were 94.84 +/- 22.3, 79.45 +/- 43.00, 70.68 +/- 35.71, 63.47 +/- 42.75 and 53.06 +/- 47.27 mg/dL, respectively, and exhibited linear dose-response. The insulin C(max) values were found to be 50.8 +/- 26.0 mU/L for placebo, 100.3 +/- 66.7 with 10 mg IN-105, 177.69 +/- 150.3 with 15 mg IN-105, 246.2 +/- 245.2 with 20 mg IN-105 and 352.5 +/- 279.3 mU/L with 30 mg of IN-105.


CONCLUSIONS
IN-105 absorption is proportional to the dose administered. The 2-h postprandial glucose excursion was reduced in a dose proportional manner. Circulating C-peptide levels were found to be suppressed in proportion to the IN-105 exposure. IN-105 reduces glucose excursion despite lower endogenous insulin secretion. IN-105 seems to have a wide therapeutic window as no clinical hypoglycaemia was observed at any of the doses studied.
Khedkar
A
A
Research and Development, Biocon Limited, Bangalore, India.
Iyer
H
H
Anand
A
A
Verma
M
M
Krishnamurthy
S
S
Savale
S
S
Atignal
A
A
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002096:C-Peptide / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008875:Middle Aged; D019518:Postprandial Period; D013607:Tablets / Q000008:administration & dosage; D016896:Treatment Outcome
D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D013607:Tablets; D008687:Metformin