PK and PD Within-Subject Variability of a Single Dose of Afrezza Inhaled Technosphere Insulin in Patients With Diabetes Mellitus Type 1 (T1DM)

Phase 1

Completed

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Drug: Technosphere Insulin SAR439065 Afrezza®

• Registration Number: NCT02485327
• Lead Sponsor: Mannkind Corporation

Brief Summary

Primary Objective:

To characterize the within-subject variability in systemic exposure pharmacokinetic (PK) to insulin of a replicate single dose of Afrezza inhaled Technosphere Insulin (TI) in T1DM patients in a euglycemic clamp setting.

To characterize the within-subject variability in the metabolic activity (pharmacodynamic \[PD\]) of a replicate single dose of Afrezza inhaled TI in T1DM patients in a euglycemic clamp setting.

Secondary Objectives:

To assess the PK characteristics of a replicate single dose of Afrezza inhaled TI in a euglycemic clamp setting.

To assess the PD characteristics of a replicate single dose of Afrezza inhaled TI in a euglycemic clamp setting.

To assess the safety and tolerability of a replicate single dose of Afrezza inhaled TI in a euglycemic clamp setting.

Detailed Description

The maximum study duration per patient is approximately 9 weeks (screening of 3 to 28 Days, treatment period of 2 days \[Periods 1 and 2\], washout period of 5 to 19 days \[between treatment period\], and end-of-study visit of 7 to 14 days after study drug administration in Period 2).

Study Timeline

• Study First Submitted: 2015-06-25
• Study First Submitted QC: 2015-06-29
• Study First Posted: 2015-06-30
• Study Start: 2015-07
• Primary Completion: 2015-11
• Study Completion: 2015-11
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-13
• Last Update Posted: 2017-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Afrezza®	Technosphere Insulin SAR439065 Afrezza®	Two-period, replicate single dose, euglycemic clamp study. There will be 2 treatment periods with a replicate administration of 1 dose of Afrezza TI (40U) in both periods. Each patient will be given a replicate administration of 1 dose level of Afrezza TI with washout duration between treatment periods (5-19 days between periods, ie, 7 to 21 days between dosing occasions).

Primary Outcome Measures

Name	Time	Method
Assessment of PK parameter: area under the serum insulin concentration time curve from time 0 to 8H (INS-AUC0-8H)	8 hours
Assessment of PD parameter: area under the glucose infusion rate curve (GIR) necessary to maintain euglycemia during the euglycemic clamp over 8 hours	8 hours

Secondary Outcome Measures

Name	Time	Method
Assessment of PK parameter: maximum Afrezza insulin serum concentration (INS-Cmax)	8 hours
Assessment of PK parameter: time to INS-Cmax (INS-tmax)	8 hours
Assessment of PD parameter: maximum smoothed GIR (GIRmax)	8 hours
Assessment of PD parameter: time to GIRmax (GIR-Tmax)	8 hours

Trial Locations

Locations (1)

Investigational Site Number 276001; 🇩🇪 Mainz, Germany