Dose-Response and Variability of Inhaled Insulin in Type 2 Diabetes

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: INH 208 U; Drug: INH 139 U; Drug: LIS 18 U; Drug: INH 69 U (low); Drug: INH 69 U (high)

• Registration Number: NCT02716610
• Lead Sponsor: Dance Biopharm Inc.

Brief Summary

Pharmacokinetic (PK) and Pharmacodynamic (PD) dose-response investigation of Dance-501 inhaled human insulin

Detailed Description

This study investigated the pharmacokinetic (PK) and pharmacodynamic (PD) properties of Dance-501, a novel inhaled human insulin liquid formulation (INH) and device. Twenty-four subjects with type 2 diabetes (T2DM) received 3 INH doses: low (69 units), medium (139 units) and high (208 units) and 1 equivalent medium dose (18 units) of subcutaneous insulin lispro (LIS).

The medium dose was repeated to determine within subject variability. PD was investigated during a 12 hour euglycemic clamp.

Study Timeline

• Study Start: 2013-10
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Status Verified: 2016-03
• Study First Submitted: 2016-03-09
• Study First Submitted QC: 2016-03-17
• Last Update Submitted: 2016-03-17
• Study First Posted: 2016-03-23
• Last Update Posted: 2016-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Type 2 diabetes mellitus treated with insulin injections at a total daily dose less than 1.2 U/kg/day.
• Body mass index 25-40 kg/m2
• Hemoglobin A1c 6.5-9.5%
• Forced vital capacity and forced expiratory volume in 1 second at least 75% of predicted normal values.
• Fasting c-peptide less than 1 nmol/L

Exclusion Criteria

• Any condition possibly affecting drug absorption from the lung, in particular subjects with decreased lung function or subjects taking bronchodilators or subjects who smoke.
• Active or chronic pulmonary disease.
• Any major disorder other than type 2 diabetes.
• Decompensated heart failure or myocardial infarction at any time or angina pectoris within the last 12 months.
• Proliferative retinopathy or maculopathy or severe neuropathy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
INH 208 U	INH 208 U	single 208 U dose administration of Dance inhaled human insulin using a high-concentration formulation (900 U/mL)
INH 139 U	INH 139 U	single 139 U dose administration of Dance inhaled human insulin using a high-concentration formulation (900 U/mL) This arm was repeated in order to evaluate intra-subject variability.
LIS 18 U	LIS 18 U	single 18 U dose administration of subcutaneous insulin lispro using a 100 U/mL formulation This arm was repeated in order to evaluate intra-subject variability.
INH 69 U (low)	INH 69 U (low)	single 69 U dose administration of Dance inhaled human insulin using a low-concentration formulation (300 U/mL)
INH 69 U (high)	INH 69 U (high)	single 69 U dose administration of Dance inhaled human insulin using a high-concentration formulation (900 U/mL)

Primary Outcome Measures

Name	Time	Method
Area under the curve for glucose infusion rate from 0-12 hours (AUGgir0-12h)	0 to 8 hours following each dose	Assessment of the linearity of the dose-response curves
Maximum glucose infusion rate (GIRmax)	up to 12 hours following each dose	Assessment of the linearity of the dose-response curves
Area under the curve for insulin from 0-8 hours (AUCins0-8h)	0 to 8 hours following each dose	Assessment of the linearity of the dose-response curves
Maximum concentration of insulin (CMaxIns)	up to 12 hours following each dose	Assessment of the linearity of the dose-response curves

Secondary Outcome Measures

Name	Time	Method
Bioavailability	0 to 8 hours following each dose	Relative delivery efficiency (FREL) of inhaled human insulin (INH) compared to subcutaneous injected insulin lispro (LIS)