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

Type 1 Diabetes Mellitus Clinical Trial

Official title:

A Randomized, Controlled, 6-treatment, 6-sequence, 6-period Cross-over Dose Response Study of 3 Single Doses of Afrezza Inhaled Technosphere Insulin and of 3 Single Doses of SC Insulin Lispro in Patients With Diabetes Mellitus Type 1 Using the Euglycemic Clamp Technique

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02470637
• Other study ID #: PDY14324
• Secondary ID: 2015-000231-33U1
• Status: Completed
• Phase: Phase 1
• First received: June 10, 2015
• Last updated: April 12, 2017
• Start date: June 2015
• Est. completion date: September 2015

Study information

• Verified date: April 2017
• Source: Mannkind Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 [ß-hCG] blood test), breastfeeding at screening and before any treatment periods (defined as positive ß-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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• SAR439065
Pharmaceutical form:dry powder insulin Route of administration: inhalation
• Insulin lispro
Pharmaceutical form:solution for injection Route of administration: subcutaneous

Locations

Country	Name	City	State
Germany	Investigational Site Number 276001	Neuss

Sponsors (1)

Lead Sponsor	Collaborator
Mannkind Corporation

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Assessment of PD parameters: Maximum smoothed glucose infusion rate (GIRmax)		24 hours
Secondary	Assessment of PD parameters: Time to GIRmax (GIR-Tmax)		24 hours
Secondary	Duration of blood glucose control (time to elevation of smoothed blood glucose profile above different prespecified clamp levels)		24 hours
Secondary	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
Secondary	Assessment of PK parameters: Baseline-corrected maximum serum concentration (INS-Cmax)		24 hours
Secondary	Assessment of PK parameters: Time to INS-Cmax (INS-Tmax)		24 hours
Secondary	Assessment of PK parameters: Area under the concentration-time curve (INS-AUClast)		24 hours
Secondary	Number of patients with adverse events		Up to 2 days