Evaluation of Safety and Diabetes Status Upon Oral Treatment With GABA in Patients With Longstanding Type-1 Diabetes

Inclusion criteria

• Informed consent given by patients according to national regulations
• Type 1 diabetes diagnosed ≥ 5 years at the time of screening
• Must have been diagnosed with Type 1-diabetes before the age of 25
• Age ≥18 and ≤50
• Fasting c-peptide levels should be in the range from not detectable levels up to <0.12 nmol/L
• For males of childbearing potential adequate contraception is as follows:

• condom (male)
• abstinence from heterosexual intercourse
• female partner using contraception as below listed:

• oral (except low-dose gestagen (lynestrenol and norethisterone)), injectable, or implanted hormonal contraceptives
• combined (estrogen and progestogen containing)
• oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation
• intrauterine device
• intrauterine hormone-releasing system (for example, progestin-releasing coil)
• bilateral tubal occlusion

Exclusion criteria

• Females of child-bearing potential
• Previous or current treatment with immunosuppressant therapy (although topical and inhalation steroids are accepted)
• Treatment with any oral or injected anti-diabetic medications other than insulin
• Patients on medications which may disturb GABA action, such as Baclofen, Valium, Acamprosate, Neurontin, or Lyrica
• HbA1c > 90 mmol/mol
• eGFR <60 ml/min
• Increased plasma concentrations of alanine aminotransferase (>0.75 μkatl/l for females or >1.1 μkat/l for males) and/or aspartate aminotransferase (>0.60 μkat/l for females or >0.75μkat/l for males).
• Known cancer disease
• Known sleeping apnea or pulmonary disorder with carbon dioxide rentention in blood
• Previous history of pancreatitis or other exocrine pancreatic disorder
• A history of epilepsy, myasthenia gravis, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles
• A history of alcohol or drug abuse
• A significant illness other than diabetes within 2 weeks prior to first dosing
• Known human immunodeficiency virus (HIV) or hepatitis
• Females who are breastfeeding
• Males not willing to use adequate contraception during the study period.
• Known hypersensitivity agains benzodiazepins or any excipients of study drugs
• Participation in other clinical trials with a new chemical entity within 3 months or 5 half-lives of the new chemical entity, whatever longest.
• Inability or unwillingness to comply with the provisions of this protocol
• Deemed by the investigator not being able to follow instructions and/or follow the study protocol or other reasons that, at the investigator's discretion, could affect the subject's current clinical condition during study procedures.