E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012601 |
E.1.2 | Term | Diabetes mellitus |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012608 |
E.1.2 | Term | Diabetes mellitus insulin-dependent |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012610 |
E.1.2 | Term | Diabetes mellitus loss of control |
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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 |
• To assess the pharmacodynamic (PD) effects of SKP-1052 and immediate-release terbutaline on nocturnal glucose levels based on mean nadir blood glucose at 0-10 hrs post-dose (21:00 hr - 07:00 hr). |
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E.2.2 | Secondary objectives of the trial |
• To assess the mean blood glucose concentration during overnight sampling at 0-10 hrs post-dose (21:00 hr - 07:00 hr) between SKP-1052, immediate-release terbutaline and placebo • To assess the time spent with nocturnal blood glucose levels < 63 mg/dL (or 3.5 mmol/L) at 0-10 hrs post-dose (21:00 hr - 07:00 hr) between SKP-1052, immediate-release terbutaline and placebo. • To assess morning blood glucose concentration at 10 hrs post-dose (07:00 hr) • To assess the safety of SKP-1052 based on number of AEs/SAEs and on morning glucose levels at 10 hrs post-dose (07:00 hr). • To compare the plasma pharmacokinetic (PK) profile between SKP-1052 and immediate-release terbutaline. • To explore the correlation of SKP-1052 pharmacokinetics with its pharmacodynamic effects on glucose levels in type 1 DM insulin treated patients (PK/PD correlation)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Clinical diagnosis of Type 1 DM and daily use of insulin therapy for at least one year. 2. Male or female subjects, aged between 18 and 50 years inclusive. 3. HbA1c <8.5% at screening. 4. Patients on insulin pumps or on a multiple basal-bolus regime with the basal insulin given once or twice daily. Basal long lasting analogue with a bolus insulin pre-meal 3 times a day or premixed insulins when one dose is given at bedtime for at least 1 month and not anticipating a change prior to the subject‘s completion of the study. 5. Normal values for thyroid-stimulating hormone (TSH), FT3 and FT4. 6. Subjects must be able to read, understand and sign the informed consent. 7. Subjects must be willing and able to comply with study requirements.
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E.4 | Principal exclusion criteria |
1. Untreated proliferative retinopathy and/or nephropathy with a serum creatinine concentration greater than upper limit of normal at screening. 2. Known coronary, cerebral or peripheral vascular disease, Hypertrophic Obstructive Cardio -Myopathy (HOCM) (previously called idiopathic hypertrophic subaortic stenosis), tachycardia, tachyarrhythmia, uncontrolled hypertension and /or autonomic neuropathy dysfunction. 3. Patients with active chest pain, shortness of breath and fatigue on exertion within the last 12 months. 4. Clinically significant abnormal safety or laboratory (hematology, biochemistry, urinalysis) screening tests as judged by the Investigator. 5. Female subjects of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive methods include sterilization, hormonal intrauterine devices, oral contraceptives, sexual abstinence or vasectomised partner). Male subjects who are sexually active and not surgically sterilised, who or whose partner are not using adequate contraceptive methods [adequate contraceptive measures include that the subject uses a condom during intercourse and that the partner practices adequate contraception (risk of pregnancy must be lower than 1%)]. 6. Presence of a significant medical disorder (including epilepsy, or any other cause of seizures, psychiatric, sleep or behavioural disorders) that in the judgment of the investigator will affect the wearing of the sensors or the completion of any aspect of the protocol. 7. Severe hypoglycaemia resulting in seizure or experienced loss of consciousness in the previous 3 months. 8. Known hypersensitivity to terbutaline. 9. Asthma which has been medically treated within 6 months before screening. 10. Treatment with systemic or inhaled corticosteroids in the last 3 months. 11. Active infection (if at the time of the scheduled visit an infection is present, the visit will be deferred). 12. Subjects with a history of HIV, hepatitis B or hepatitis C. 13. Current treatment with oral and topical (eye) B-blockers and use of other medications, which in the judgment of the investigator would be a contraindication to participation in the study. 14. Treatment with ephedrine, phenylephrine, phenylpropanolamine, or pseudoephedrine 48 hours prior to the visit (if used in the 48 hours prior to the scheduled visit, the visit will be deferred). 15. Anticipating a significant change in exercise regimen between visits (i.e. starting or stopping an organised sport). 16. Significant blood loss (more than 500 mL) within the last 3 months prior to screening. 17. Significant history of alcoholism or drug/chemical abuse or positive result alcohol breath test at screening visit. 18. Participated in another investigational study where the study drug was received within 90 days prior to the Screening visit.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Mean nadir blood glucose concentration at time frame: 0-10 hrs post-dose (21:00 hr – 07:00 hr). |
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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 | No |
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 | Yes |
E.7.1.3.1 | Other trial type description |
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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 | No |
E.8.1.3 | Single blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
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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Last visit of last subject |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |