PK and PD Within-Subject Variability of a Single Dose of Afrezza Inhaled Technosphere Insulin in Patients With Diabetes Mellitus Type 1 (T1DM)

NCT02485327 | Completed Phase 1

• 3 other identifiers: PDY143292015-001008-74U1111-1168-4442
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To characterize the within-subject variability in systemic exposure pharmacokinetic (PK) to insulin of a replicate single dose of Afrezza inhaled Technosphere Insulin (TI) in T1DM patients in a euglycemic clamp setting. To characterize the within-subject variability in the metabolic activity (pharmacodynamic \[PD\]) of a replicate single dose of Afrezza inhaled TI in T1DM patients in a euglycemic clamp setting. Secondary Objectives: To assess the PK characteristics of a replicate single dose of Afrezza inhaled TI in a euglycemic clamp setting. To assess the PD characteristics of a replicate single dose of Afrezza inhaled TI in a euglycemic clamp setting. To assess the safety and tolerability of a replicate single dose of Afrezza inhaled TI in a euglycemic clamp setting.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• Assessment of PK parameter: area under the serum insulin concentration time curve from time 0 to 8H (INS-AUC0-8H)

  8 hours

• Assessment of PD parameter: area under the glucose infusion rate curve (GIR) necessary to maintain euglycemia during the euglycemic clamp over 8 hours

  8 hours

Secondary Outcomes (4)

• Assessment of PK parameter: maximum Afrezza insulin serum concentration (INS-Cmax)

  8 hours

• Assessment of PK parameter: time to INS-Cmax (INS-tmax)

  8 hours

• Assessment of PD parameter: maximum smoothed GIR (GIRmax)

  8 hours

• Assessment of PD parameter: time to GIRmax (GIR-Tmax)

  8 hours

Study Arms (1)

Afrezza®

EXPERIMENTAL

Two-period, replicate single dose, euglycemic clamp study. There will be 2 treatment periods with a replicate administration of 1 dose of Afrezza TI (40U) in both periods. Each patient will be given a replicate administration of 1 dose level of Afrezza TI with washout duration between treatment periods (5-19 days between periods, ie, 7 to 21 days between dosing occasions).

Drug: Technosphere Insulin SAR439065 Afrezza®

Interventions

Technosphere Insulin SAR439065 Afrezza® DRUG

Pharmaceutical form: dry powder Route of administration: oral inhalation

Also known as: Afrezza®

Afrezza®

Eligibility Criteria

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

You may qualify if:

• Body weight between 50 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 T1DM 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).
• Normal vital signs after at least 10 minutes resting in supine position:
• mmHg \<systolic blood pressure (SBP) \<150 mmHg.
• mmHg \<diastolic blood pressure (DBP) \<95 mmHg.
• bpm \<heart rate (HR) \<90 bpm.
• Normal standard 12-lead electrocardiogram (ECG) after at least 10 minutes resting in supine position; 120 ms \<PR \<220 ms, QRS \<120 ms, QTc ≤450 ms if male, ≤470 ms if female.
• Laboratory parameters within the normal range (or defined screening threshold for the Investigator site), unless the Investigator considers an abnormality to be clinically irrelevant for diabetes patients; however serum creatinine should be strictly below the upper laboratory norm; alkaline phosphatase, hepatic enzymes (aspartate aminotransferase, alanine aminotransferase), and total bilirubin (unless the patient has documented Gilbert syndrome) should not be above 1.5 x upper limit of normal (ULN).
• Women of childbearing potential (less than 2 years postmenopausal or not surgically sterile for more than 3 months), must have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test at screening and a negative urine β-HCG pregnancy test at Day 1 in all treatment periods (TPs) and must use a highly effective method of birth control, which is defined as those which result in a low failure rate (ie, less than 1% per year) according to the Note for guidance on nonclinical safety studies for the conduct of human clinical trials for pharmaceuticals (CPMP/ICH/286/95, modifications). During the entire study female subjects of childbearing potential must use 2 independent methods of contraception, eg, diaphragm and spermicide-coated condom. The use of a condom and spermicidal creams is not sufficiently reliable. For postmenopausal women with presence of less than 2 years post menopausal, and not surgically sterile for more than 3 months, the hormonal status will be determined (follicle-stimulating hormone \[FSH\] \>30 IU/L).
• Having given written informed consent prior to undertaking any study-related procedure.
• Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national (German) laws in force relating to biomedical research.
• Not under any administrative or legal supervision.

You may not qualify if:

• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic (apart from T1DM), hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness.
• 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 headaches and/or migraine, recurrent nausea and/or vomiting (more than twice a month).
• Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥20 mmHg within 3 minutes when changing from supine to standing position.
• Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
• Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol.
• History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day).
• Excessive consumption of beverages containing xanthine bases (more than 4 cups or glasses per day).
• If female, pregnancy (defined as positive β-HCG blood test), breastfeeding at screening and before any treatment periods (defined as positive β-HCG urine test).
• Any vaccination within the last 28 days.
• Any patient who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development.
• Any patient who cannot be contacted in case of emergency.
• Any patient who is the Investigator or any sub-Investigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in conducting the study.
• Positive result on any of the following tests: hepatitis B surface antigen (HBs Ag), antihepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab).
• Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, and cotinine).

Sponsors & Collaborators

• Mannkind Corporation: lead

Study Sites (1)

Investigational Site Number 276001

Mainz, 55116, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin

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)

Proinsulin; 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2015
• First Posted: June 30, 2015
• Study Start: July 1, 2015
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: March 15, 2017

Record last verified: 2017-03

Locations

DE (1)