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

NCT ID: NCT02470637

Last Updated: 2017-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2015-09-30

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.

Conditions

Type 1 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

SAR439065 + 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)

Group Type: EXPERIMENTAL

SAR439065

Intervention Type: DRUG

Pharmaceutical form:dry powder insulin

Route of administration: inhalation

Insulin lispro

Intervention Type: DRUG

Pharmaceutical form:solution for injection

Route of administration: subcutaneous

Interventions

SAR439065

Pharmaceutical form:dry powder insulin

Route of administration: inhalation

Intervention Type: DRUG

Insulin lispro

Pharmaceutical form:solution for injection

Route of administration: subcutaneous

Intervention Type: DRUG

Other Intervention Names

Afrezza Technosphere insulin; Humalog

Eligibility Criteria

Inclusion Criteria

• Male or female patients, between 18 and 65 years of age, inclusive, with diabetes mellitus type 1 for more than one year, as defined by the American Diabetes Association.
• Total insulin dose of <1.0 U/kg/day.
• Body weight between 50.0 and 95 kg, inclusive, body mass index between 18.5 and 29 kg/m², inclusive.
• Fasting serum C-peptide <0.3 nmol/L.
• Glycohemoglobin (HbA1c) ≤75 mmol/mol (≤9%).
• Stable insulin regimen for at least 2 months prior to study (with respect to safety of the patient and scientific integrity of the study).
• Certified as otherwise healthy for type 1 diabetes mellitus patient by assessment of medical history and physical examination (cardiovascular system, chest and lungs, thyroid, abdomen, nervous system, skin and mucosae, and musculoskeletal system), unless the Investigator considers any abnormality to be clinically irrelevant and not interfering with the conduct of the study (with respect to safety of the subject and scientific integrity of the study).
• Having given written informed consent prior to undertaking any study-related procedure.
• Non-smoking at least for the last 6 months before screening (to be confirmed by urine cotinine <500 µg/L).
• Pulmonary function test at screening: forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) >70% of the individual prediction according to the equation of the Third National Health and Nutrition Examination Survey (NHANES III).

Exclusion Criteria

• Severe hypoglycemia resulting in coma/seizures or requiring assistance of another person, and/or hospitalization for diabetic ketoacidosis in the last 6 months before screening visit.
• Frequent severe headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
• Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
• History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day).
• If female, pregnancy (defined as positive beta-human chorionic gonadotropin [β-hCG] blood test), breastfeeding at screening and before any treatment periods (defined as positive β-hCG urine test).
• Any medication (including St John's Wort) within 14 days before inclusion or within 5 times the elimination half-life or PD half-life of the medication, with the exception of insulins, thyroid hormones, lipid-lowering, and antihypertensive drugs and if female with the exception of hormonal contraception or menopausal hormone replacement therapy; any vaccination within 28 days before inclusion.
• Presence or history of any acute or chronic obstructive bronchopulmonary disease including chronic obstructive pulmonary disease, asthma, and cancer.
• Upper respiratory tract infection within 8 weeks before screening.
• Known hypersensitivity to insulin lispro or Afrezza Technosphere insulin and excipients.
• Inability, in the opinion of the Principal Investigator or a designee, to adequately inhale Afrezza powder.
• Any history or presence of deep leg vein thrombosis or a frequent appearance of deep leg vein thrombosis in first-degree relatives (parents, siblings, or children).
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mannkind Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 276001

Neuss, , Germany

Countries

Germany

References

Grant M, Heise T, Baughman R. Comparison of Pharmacokinetics and Pharmacodynamics of Inhaled Technosphere Insulin and Subcutaneous Insulin Lispro in the Treatment of Type 1 Diabetes Mellitus. Clin Pharmacokinet. 2022 Mar;61(3):413-422. doi: 10.1007/s40262-021-01084-0. Epub 2021 Nov 13.

Reference Type: DERIVED

PMID: 34773608 (View on PubMed)

Other Identifiers

2015-000231-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1166-5431

Identifier Type: OTHER

Identifier Source: secondary_id

PDY14324

Identifier Type: -

Identifier Source: org_study_id