Type 1 Diabetes MellitusPhase 1NCT02485327
PK and PD Within-Subject Variability of a Single Dose of Afrezza Inhaled Technosphere Insulin in Patients With Diabetes Mellitus Type 1 (T1DM)
A Phase 1 study testing Technosphere Insulin SAR439065 Afrezza® in people with Type 1 Diabetes Mellitus, run by Mannkind Corporation at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Technosphere Insulin SAR439065 Afrezza®
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2015to Nov 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 95 mmHg <systolic blood pressure (SBP) <150 mmHg.
- 45 mmHg <diastolic blood pressure (DBP) <95 mmHg.
- 50 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.
- Nonsmoking at least for the last 6 months before screening (to be confirmed by serum cotinine <25 µg/L or urine <500 µg/L).
- Pulmonary function test at screening: forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) greater than or equal to 70% of the individual prediction according to the equation of the Third National Health and Nutrition Examination Survey (NHANES III).
Who cannot join
- 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).
- Blood donation, any volume, within 3 months before inclusion.
- 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.
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- 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 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 insulin, stable treatment (at least 2 months) with thyroid hormones, lipid-lowering and antihypertensive drugs and if female with the exception of hormonal contraception or menopausal hormone replacement therapy.
- 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 in the exclusion period of a previous study according to applicable regulations.
- 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).
- Positive alcohol test.
- Presence or history of any acute or chronic obstructive bronchopulmonary disease (COPD) including asthma, cancer.
- Upper respiratory tract infection within 8 weeks before screening.
- Known hypersensitivity to Afrezza TI 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, 2 Replicate Single Dose Euglycemic Glucose-Clamp Trial to Characterize PK and PD Within-Subject Variability of a Single Dose of Afrezza Inhaled Technosphere Insulin in Patients With Diabetes Mellitus Type 1 (T1DM)
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.
Read more
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.
Read the detailed description
The maximum study duration per patient is approximately 9 weeks (screening of 3 to 28 Days, treatment period of 2 days [Periods 1 and 2], washout period of 5 to 19 days [between treatment period], and end-of-study visit of 7 to 14 days after study drug administration in Period 2).
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Technosphere Insulin SAR439065 Afrezza®
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Technosphere Insulin SAR439065 Afrezza®Drug
Also called Afrezza®
Pharmaceutical form: dry powder
Route of administration: oral inhalation
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Technosphere Insulin SAR439065 Afrezza® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of PK parameter: area under the serum insulin concentration time curve from time 0 to 8H (INS-AUC0-8H)
Measured: 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
Measured: 8 hours
Secondary outcomes (4)
Assessment of PK parameter: maximum Afrezza insulin serum concentration (INS-Cmax)
Measured: 8 hours
Assessment of PK parameter: time to INS-Cmax (INS-tmax)
Measured: 8 hours
Assessment of PD parameter: maximum smoothed GIR (GIRmax)
Measured: 8 hours
Assessment of PD parameter: time to GIRmax (GIR-Tmax)
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2015 (estimated)
- Study startJul 2015
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mannkind Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02485327
- Sponsor's protocol ID
- PDY14329
- Other IDs
- 2015-001008-74, U1111-1168-4442, 2015
- Status last verified
- Mar 2017
- First submitted
- 25 Jun 2015
- Last updated
- 15 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, 2 Replicate Single Dose Euglycemic Glucose-Clamp Trial to Characterize PK and PD Within-Subject Variability of a Single Dose of Afrezza Inhaled Technosphere Insulin in Patients With Diabetes Mellitus Type 1 (T1DM)
- ClinicalTrials.gov ID
- NCT02485327
- Acronym / sponsor ID
- PDY14329
- Conditions
- Type 1 Diabetes Mellitus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Mannkind CorporationIndustry (pharma, biotech, devices)
- Study start
- Jul 2015
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 30 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The maximum study duration per patient is approximately 9 weeks (screening of 3 to 28 Days, treatment period of 2 days [Periods 1 and 2], washout period of 5 to 19 days [between treatment period], and end-of-study visit of 7 to 14 days after study drug administration in Period 2).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Afrezza® | Experimental | Drug: Technosphere Insulin SAR439065 Afrezza®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). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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).
Key exclusion criteria (25 listed)
- 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).
- Blood donation, any volume, within 3 months before inclusion.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Technosphere Insulin SAR439065 Afrezza®Also: Afrezza®Pharmaceutical form: dry powder Route of administration: oral inhalation | Drug | Afrezza® |
Primary outcome
Assessment of PK parameter: area under the serum insulin concentration time curve from time 0 to 8H (INS-AUC0-8H)
Time frame: 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
Time frame: 8 hours
4 secondary outcomes
Assessment of PK parameter: maximum Afrezza insulin serum concentration (INS-Cmax)
Time frame: 8 hours
Assessment of PK parameter: time to INS-Cmax (INS-tmax)
Time frame: 8 hours
Assessment of PD parameter: maximum smoothed GIR (GIRmax)
Time frame: 8 hours
Assessment of PD parameter: time to GIRmax (GIR-Tmax)
Time frame: 8 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Technosphere Insulin SAR439065 Afrezza® in people with Type 1 Diabetes Mellitus, run by Mannkind Corporation at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of PK parameter: area under the serum insulin concentration time curve from time 0 to 8H (INS-AUC0-8H) (time frame: 8 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2017.