This is a Phase I study, involving healthy subjects. The study is designed as a "Proof of Concept" to evaluate oromucosal delivery of insulin, contained in a mucoadhesive wafer. The study population in this clinical study will not benefit from the treatment. Orosomucosal delivery of insulin may be of benefit to patients with Diabetes Mellitus. E10
Conditions
Interventions
Group 1: Lingual/palatal OR Gingival placebo wafers (depending on the results of Part 1 of the study) plus subcutaneously administered insulin (0.2 mL, 7.5 IU)
N=12 healthy subjects.
Group 2: Lingual/palatal OR Gingival placebo wafers (depending on the results of Part 1 of the study) plus subcutaneously administered physiological saline (0.2 mL)
N=12 healthy subjects.
Sponsors
LTS Lohmann Therapie-Systeme AG
Eligibility
Sex/Gender
Male
Age
18 Years to 45 Years
Inclusion criteria
Inclusion criteria: Male subjects of any ethnic origin between 18 and 45 years of age (inclusive); Non-smokers; In good general physical health, determined by medical history (including exclusion of first-degree family diabetes); Physical examination, electrocardiogram (ECG), vital signs, clinical laboratory tests; Body Mass Index within 19 to 28 kg/m2 and body weight within 69.4 to 80.6 kg (75 kg ± 7.5%); Fasting venous blood glucose between 70 and 110 mg/dL (inclusive).
Exclusion criteria
Exclusion criteria: Subjects with tendency for gum bleeding, oromucosal lesions or other oromucosal diseases; Subjects with a clinical history of allergic reactions against p-Hydroxy benzoic acid esters (PHB-esters); Hypersensitivity to any of the ingredients of the investigational medicinal product; Any history of alcohol or drug abuse; Any history of chronic gastritis or peptic ulcers; Any history of chronic or recurrent metabolic, renal, hepatic, pulmonary, gastrointestinal, neurological (esp. history of epileptic seizures), endocrinological, immunological, psychiatric or cardiovascular disease, myopathies and bleeding tendency; Blood donation within 30 days prior to inclusion in this study; Laboratory values outside the reference range that are of clinical relevance (e.g., suggesting an unknown disease and requiring further clinical evaluation assessed by the investigator) especially aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (gamma-GT).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 2 of the study: "Proof of concept" by comparing insulin delivery after oromucosal application of insulin-containing wafers (data from Part 1) with subcutaneous injection of insulin and placebo. Glucose clamp: Constant insulin infusion: up to 5 h after start administration with an infusion rate of up to 0.15 mU/kg min. Glucose sampling (capillary blood sampling): approximately every 10 to 15 min for approximately 50 min prior to dosing (at least 5 samples), every 5 min during wafer application (at least 13 samples), after the end of the administration period every 15 to 30 min for up to 5 h after start of wafer administration (at least 16 samples). Venous blood sampling for pharmacokinetics: Blood samples (2.7 mL) for the determination of insulin and C-peptide concentrations in serum at -2.0, -1.5, -1.0, -0.5, 0 (=start of wafer administration), 0,083 (5 min), 0,167 (10 min), 0.25 (15 min), 0.33 (20 min), 0.42 (25 min), 0.5 (30 min), 0.75 (45 min), 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0 h after start of administration (21 blood samples). Venous blood sampling for pharmacodynamics: Blood samples (2.7 mL) for the determination of glucose in plasma will be taken at -2.0, -1.5, -1.0, -0.5, 0 (=start of wafer administration), 0.083 (5 min), 0.167 (10 min), 0.25 (15 min), 0.33 (20 min), 0.42 (25 min), 0.5 (30 min), 0.75 (45 min), 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0 after start of administration (21 blood samples). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objective is to assess the safety and tolerability of oromucosal application of insulin containing wafers. Adverse events, physical examination, clinical laboratory, vital signs, ECG, local and overall tolerability. | — |
Countries
Germany
Contacts
Public ContactWolfgang Timmer
CRS Clinical Research Services Mannheim GmbH
Outcome results
None listed