E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assessment of the inter- and intra subject variability (based on AUCINS,0-10h , CMAX,INS , AUCGIR,0-10h , and GIRMAX ) of Dance 501 Human Insulin Inhalation Solution (INH) administered with the Dance 501 Inhaler |
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E.2.2 | Secondary objectives of the trial |
• Assessment of the pharmacokinetic (PK) and pharmacodynamic (PD) responses of INH
• Assessment of the relative efficiency of INH compared to subcutaneous (s.c.) insulin lispro
• Safety and tolerability of INH |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female subjects 18 to 55 years of age (both inclusive) with T1DM
• HbA1c ≤ 9.0% inclusive
• Subjects with T1DM taking 2 or more injections of insulin daily or continuous s.c. insulin infusion for at least 6 months prior to screening
• Current total daily insulin treatment < 1.2 (I)U/kg/day
• BMI ≥ 18.5 and ≤ 30 kg/m2
• Non-smoker for ≥ 5 years prior to screening, confirmed by a negative screening urine cotinine test
• Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) ≥ 75 % of predicted normal values for race, age, gender and height
• Fasting C-peptide ≤ 0.30 nmol/L |
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E.4 | Principal exclusion criteria |
• Any condition possibly affecting drug absorption from the lung, in particular subjects with decreased lung
function, any active pulmonary disease or taking bronchodilators
• Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer
• Any history or presence of clinically relevant comorbidity (with the exception of conditions associated with
diabetes mellitus), or signs of acute illness, as judged by the Investigator
• Recurrent severe hypoglycemia
• Proliferative retinopathy or maculopathy or severe autonomic neuropathy
• Current treatment with medications that may interfere with glucose metabolism
• Clinical significant abnormal findings during physical examination, laboratory and ECG results at screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Pharmacokinetic Endpoints:
1. AUCINS, 0-10h: Area under insulin (INS) and insulin lispro curve
2. CMAX INS: Maximum observed insulin or insulin lispro concentration
Primary Pharmacodynamic Endpoints:
1. AUCGIR,0-10h : Area under the glucose infusion rate-time curve
2. GIRMAX: Maximum glucose infusion rate
Safety endpoints:
• Adverse Events (including adverse device effects and hypoglycemic episodes)
• Clinical laboratory measures
• Physical examinations
• Vital signs
• Electrocardiogram (ECG)
• Spirometry
• Insulin antibodies |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Pharmacokinetic Endpoints:
1. from t= 0 to 10 hours
2. maximum observed concentration
Primary Pharmacodynamic Endpoints:
1. from t=0 to 10 hours
2. maximum observed GIR
Safety endpoints:
ongoing |
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E.5.2 | Secondary end point(s) |
Secondary Pharmacokinetic Endpoints:
• AUCINS 0-1h: Area under insulin (INS) and insulin lispro curve from t= 0 to 1hour
• AUCINS 0-2h: Area under insulin (INS) and insulin lispro curve from t= 0 to 2hours
• AUCINS 0-8h: Area under insulin (INS) and insulin lispro curve from t= 0 to 8hours
• tMAX INS: Time to maximum insulin concentration
• FREL: Relative efficiency = dose corrected ratio of AUCINS, 0-10h for INH and s.c. insulin lispro
• Onset of appearance: time from trial product administration until first time serum insulin concentration >
LLOQ (in case of different LLOQ values further restrictions will be defined in section 13)
• MRTINS: mean residence time of insulin
• t50%-INS(early), time to half-maximum before Cmax
• t50%-INS(late), time to half-maximum after Cmax
Secondary Pharmacodynamic Endpoints:
• AUCGIR 0-1h : Area under the glucose infusion rate-time curve from t=0 to 1hour
• AUCGIR 0-2h : Area under the glucose infusion rate-time curve from t=0 to 2hours
• AUCGIR 0-8h : Area under the glucose infusion rate-time curve from t=0 to 8hours
• tGIRMAX: Time to maximum glucose infusion rate
• GREL: Relative biopotency = dose corrected ratio of AUCGIR,0-10h for INH and s.c. insulin lispro
• Duration of action
• t50%-GIR(early), time to half-maximum glucose infusion rate before GIRmax
• t50%-GIR(late), time to half-maximum glucose infusion rate after GIRmax |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
as detailed in section E.5.2 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |