AzTrials
AzTrials

Type 1 Diabetes MellitusPhase 1NCT02470637

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 Phase 1 study testing SAR439065 and Insulin lispro in people with Type 1 Diabetes Mellitus, run by Mannkind Corporation at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. 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?
SAR439065 and Insulin lispro
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteGermany
Study dates
Jun 2015to Sep 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

  • 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).
Show all 10Show fewer
  • 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).

Who cannot join

  • 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.
Show all 12Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Investigational Site Number 276001

    Neuss, 41460

Other trials in Germany

About this study

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

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.

Read more

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.

Read the 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.

Being tested
SAR439065, Insulin lispro
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.

  • SAR439065Drug

    Also called Afrezza Technosphere insulin

    Pharmaceutical form:dry powder insulin

    Route of administration: inhalation

  • Insulin lisproDrug

    Also called Humalog

    Pharmaceutical form:solution for injection

    Route of administration: subcutaneous

Study groups in NCT02470637
Study groupRoleWhat they receive
SAR439065 + insulin lisproExperimental1 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)
Receives: Drug: SAR439065; Drug: Insulin lispro

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: 24 hours

Secondary outcomes (8)

  1. Assessment of PD parameters: Maximum smoothed glucose infusion rate (GIRmax)

    Measured: 24 hours

  2. Assessment of PD parameters: Time to GIRmax (GIR-Tmax)

    Measured: 24 hours

  3. Duration of blood glucose control (time to elevation of smoothed blood glucose profile above different prespecified clamp levels)

    Measured: 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)

    Measured: 24 hours

  5. Assessment of PK parameters: Baseline-corrected maximum serum concentration (INS-Cmax)

    Measured: 24 hours

  6. Assessment of PK parameters: Time to INS-Cmax (INS-Tmax)

    Measured: 24 hours

  7. Assessment of PK parameters: Area under the concentration-time curve (INS-AUClast)

    Measured: 24 hours

  8. Number of patients with adverse events

    Measured: Up to 2 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2015 (estimated)
  2. Study startJun 2015
  3. Primary completionSep 2015
  4. Study completionSep 2015

Resources

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
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02470637
Sponsor's protocol ID
PDY14324
Other IDs
2015-000231-33, U1111-1166-5431, 2015
Status last verified
Apr 2017
First submitted
10 Jun 2015
Last updated
13 Apr 2017
Results posted
No
Data monitoring committee
No

Publications

  • Grant M, Heise T, Baughman R. Comparison of Pharmacokinetics and Pharmacodynamics of Inhaled Technosphere Insulin and Subcutaneous Insulin Lispro in the Treatment of Type 1 Diabetes Mellitus. Clin Pharmacokinet. 2022 Mar;61(3):413-422. doi: 10.1007/s40262-021-01084-0. Epub 2021 Nov 13.

    PubMed 34773608

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SAR439065 and Insulin lispro 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 10 inclusion and 12 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 13 Apr 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 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02470637, which also lists 1 linked publication.

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 13 Apr 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in