Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02470637
Recruitment Status : Completed
First Posted : June 12, 2015
Last Update Posted : April 13, 2017
Sponsor:
Information provided by (Responsible Party):
Mannkind Corporation

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.


Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Drug: SAR439065 Drug: Insulin lispro Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Study Start Date : June 2015
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

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)
Drug: SAR439065

Pharmaceutical form:dry powder insulin

Route of administration: inhalation

Other Name: Afrezza Technosphere insulin

Drug: Insulin lispro

Pharmaceutical form:solution for injection

Route of administration: subcutaneous

Other Name: Humalog




Primary Outcome Measures :
  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) [ Time Frame: 24 hours ]

Secondary Outcome Measures :
  1. Assessment of PD parameters: Maximum smoothed glucose infusion rate (GIRmax) [ Time Frame: 24 hours ]
  2. Assessment of PD parameters: Time to GIRmax (GIR-Tmax) [ Time Frame: 24 hours ]
  3. Duration of blood glucose control (time to elevation of smoothed blood glucose profile above different prespecified clamp levels) [ Time Frame: 24 hours ]
  4. 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 ]
  5. Assessment of PK parameters: Baseline-corrected maximum serum concentration (INS-Cmax) [ Time Frame: 24 hours ]
  6. Assessment of PK parameters: Time to INS-Cmax (INS-Tmax) [ Time Frame: 24 hours ]
  7. Assessment of PK parameters: Area under the concentration-time curve (INS-AUClast) [ Time Frame: 24 hours ]
  8. Number of patients with adverse events [ Time Frame: Up to 2 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02470637


Locations
Layout table for location information
Germany
Investigational Site Number 276001
Neuss, Germany, 41460
Sponsors and Collaborators
Mannkind Corporation
Investigators
Layout table for investigator information
Study Director: Clinical Sciences & Operations Sanofi
Layout table for additonal information
Responsible Party: Mannkind Corporation
ClinicalTrials.gov Identifier: NCT02470637    
Other Study ID Numbers: PDY14324
2015-000231-33 ( EudraCT Number )
U1111-1166-5431 ( Other Identifier: UTN )
First Posted: June 12, 2015    Key Record Dates
Last Update Posted: April 13, 2017
Last Verified: April 2017
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Insulin, Globin Zinc
Insulin Lispro
Hypoglycemic Agents
Physiological Effects of Drugs