Single Dose Clamp Study to Evaluate Concentration-time Profile and Metabolic Activity of 3 Dose Levels of Afrezza and 3 Dose Levels of Insulin Lispro in Patients With Type 1 Diabetes Mellitus

Phase 1

Completed

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Drug: SAR439065; Drug: Insulin lispro

• Registration Number: NCT02470637
• Lead Sponsor: Mannkind Corporation

Brief Summary

Primary Objective:

To assess the dose-response pattern of the glucose consumption (GIR-AUC0-end) of 3 different single doses of Afrezza inhaled Technosphere insulin and of 3 single doses of subcutaneous (SC) insulin lispro in a euglycemic clamp setting.

Secondary Objectives:

To assess the dose proportionality of insulin exposure (INS-AUClast) of 3 different single doses of Afrezza inhaled Technosphere insulin and of 3 single doses of SC insulin lispro in a euglycemic clamp setting.

To assess the pharmacodynamic (PD) characteristics of 3 different single doses of Afrezza inhaled Technosphere insulin and of 3 single doses of SC insulin lispro in a euglycemic clamp setting.

To assess the pharmacokinetic (PK) characteristics of 3 different single doses of Afrezza inhaled Technosphere insulin and of 3 single doses of SC insulin lispro in a euglycemic clamp setting.

To assess the safety and tolerability of 3 different single doses of Afrezza inhaled Technosphere insulin.

Detailed Description

The total study duration for one patient is approximately 6.7 to 22.7 weeks (minimum to maximum duration, excluding screening). The duration of the study includes a screening period of 3 to 28 days (D -28 to D -3), 6 treatment periods of 1 or 2 days each (1 overnight stay), a washout period of 7 to 28 days (preferentially 7 days between consecutive dosing), and an end-of-study visit of 7 to 14 days after the last study drug administration.

Study Timeline

• Study Start: 2015-06
• Study First Submitted: 2015-06-10
• Study First Submitted QC: 2015-06-11
• Study First Posted: 2015-06-12
• Primary Completion: 2015-09
• Study Completion: 2015-09
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-12
• Last Update Posted: 2017-04-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
SAR439065 + insulin lispro	SAR439065	1 of 6 sequences with single administration of 3 dose levels of SAR439065 (Afrezza Technosphere insulin) and 3 dose levels of insulin lispro with a washout duration between dosing days (7 to 28 days)
SAR439065 + insulin lispro	Insulin lispro	1 of 6 sequences with single administration of 3 dose levels of SAR439065 (Afrezza Technosphere insulin) and 3 dose levels of insulin lispro with a washout duration between dosing days (7 to 28 days)

Primary Outcome Measures

Name	Time	Method
Assessment of PD parameter: Area under the glucose infusion rate curve within 24 hours after administration of the investigational medicinal product or until administration of rescue insulin (GIR-AUC0-end)	24 hours

Secondary Outcome Measures

Name	Time	Method
Assessment of PD parameters: Time to GIRmax (GIR-Tmax)	24 hours
Assessment of PK parameters: Time to INS-Cmax (INS-Tmax)	24 hours
Assessment of PK parameters: Baseline-corrected maximum serum concentration (INS-Cmax)	24 hours
Number of patients with adverse events	Up to 2 days
Assessment of PD parameters: Maximum smoothed glucose infusion rate (GIRmax)	24 hours
Assessment of PK parameters: Area under the baseline-corrected serum insulin concentration-time curve over 24 hours or until administration of rescue insulin (INS-AUClast)	24 hours
Duration of blood glucose control (time to elevation of smoothed blood glucose profile above different prespecified clamp levels)	24 hours
Assessment of PK parameters: Area under the concentration-time curve (INS-AUClast)	24 hours

Trial Locations

Locations (1)

Investigational Site Number 276001; 🇩🇪 Neuss, Germany