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

NCT02470637 | Completed Phase 1

• 3 other identifiers: PDY143242015-000231-33U1111-1166-5431
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Assessment of PD parameters: Maximum smoothed glucose infusion rate (GIRmax)

  24 hours

• Assessment of PD parameters: Time to GIRmax (GIR-Tmax)

  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 baseline-corrected serum insulin concentration-time curve over 24 hours or until administration of rescue insulin (INS-AUClast)

  24 hours

• Assessment of PK parameters: Baseline-corrected maximum serum concentration (INS-Cmax)

  24 hours

Study Arms (1)

SAR439065 + insulin lispro

EXPERIMENTAL

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)

Drug: SAR439065; Drug: Insulin lispro

Interventions

SAR439065 DRUG

Pharmaceutical form:dry powder insulin Route of administration: inhalation

Also known as: Afrezza Technosphere insulin

SAR439065 + insulin lispro

Insulin lispro DRUG

Pharmaceutical form:solution for injection Route of administration: subcutaneous

Also known as: Humalog

SAR439065 + insulin lispro

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Mannkind Corporation: lead

Study Sites (1)

Investigational Site Number 276001

Neuss, 41460, Germany

Location

Related Publications (1)

• 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.

  PMID: 34773608 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin Lispro

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: June 12, 2015
• Study Start: June 1, 2015
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: April 13, 2017

Record last verified: 2017-04

Locations

DE (1)