- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02470637
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
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Neuss, Germany, 41460
- Investigational Site Number 276001
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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)
|
Pharmaceutical form:dry powder insulin Route of administration: inhalation
Other Names:
Pharmaceutical form:solution for injection Route of administration: subcutaneous
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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)
Time Frame: 24 hours
|
24 hours
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Assessment of PD parameters: Maximum smoothed glucose infusion rate (GIRmax)
Time Frame: 24 hours
|
24 hours
|
Assessment of PD parameters: Time to GIRmax (GIR-Tmax)
Time Frame: 24 hours
|
24 hours
|
Duration of blood glucose control (time to elevation of smoothed blood glucose profile above different prespecified clamp levels)
Time Frame: 24 hours
|
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)
Time Frame: 24 hours
|
24 hours
|
Assessment of PK parameters: Baseline-corrected maximum serum concentration (INS-Cmax)
Time Frame: 24 hours
|
24 hours
|
Assessment of PK parameters: Time to INS-Cmax (INS-Tmax)
Time Frame: 24 hours
|
24 hours
|
Assessment of PK parameters: Area under the concentration-time curve (INS-AUClast)
Time Frame: 24 hours
|
24 hours
|
Number of patients with adverse events
Time Frame: Up to 2 days
|
Up to 2 days
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PDY14324
- 2015-000231-33 (EudraCT Number)
- U1111-1166-5431 (Other Identifier: UTN)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Type 1 Diabetes Mellitus
-
SanofiCompletedType 1 Diabetes Mellitus-Type 2 Diabetes MellitusHungary, Russian Federation, Germany, Poland, Japan, United States, Finland
-
University of Colorado, DenverMassachusetts General Hospital; Beta Bionics, Inc.CompletedDiabetes Mellitus, Type 1 | Type 1 Diabetes | Diabetes type1 | Type 1 Diabetes Mellitus | Autoimmune Diabetes | Diabetes Mellitus, Insulin-Dependent | Juvenile-Onset Diabetes | Diabetes, Autoimmune | Insulin-Dependent Diabetes Mellitus 1 | Diabetes Mellitus, Insulin-Dependent, 1 | Diabetes Mellitus, Brittle | Diabetes Mellitus, Juvenile-Onset and other conditionsUnited States
-
University of California, San FranciscoJuvenile Diabetes Research FoundationCompletedType 1 Diabetes Mellitus | Diabetes Mellitus, Type I | Insulin-Dependent Diabetes Mellitus 1 | Diabetes Mellitus, Insulin-Dependent, 1 | IDDMUnited States, Australia
-
AstraZenecaCompletedType 2 Diabetes Mellitus | Type 1 Diabetes MellitusUnited States
-
Capillary Biomedical, Inc.TerminatedType 1 Diabetes | Type 1 Diabetes Mellitus | Diabetes Mellitus, Type I | Diabetes Mellitus, Insulin-Dependent, 1 | IDDMAustria
-
National Institute of Allergy and Infectious Diseases...PPD; Rho Federal Systems Division, Inc.; Immune Tolerance Network (ITN)CompletedType 1 Diabetes Mellitus | T1DM | T1D | New-onset Type 1 Diabetes MellitusUnited States, Australia
-
Shanghai Changzheng HospitalRecruitingBrittle Type 1 Diabetes MellitusChina
-
Capillary Biomedical, Inc.CompletedDiabetes Mellitus, Type 1 | Type 1 Diabetes | Type 1 Diabetes Mellitus | Diabetes Mellitus, Insulin-Dependent, 1Australia
-
Spiden AGDCB Research AGRecruitingType 1 Diabetes Mellitus | Type 1 Diabetes Mellitus With Hypoglycemia | Type 1 Diabetes Mellitus With HyperglycemiaSwitzerland
-
Hoffmann-La RocheRoche DiagnosticsCompletedDiabetes Mellitus Type 2, Diabetes Mellitus Type 1Germany
Clinical Trials on SAR439065
-
Mannkind CorporationCompleted