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

A Phase I/II, 3-Arm, Open Label, Single Centre Study to Investigate the Safety and Effect of Oral GABA Therapy on Beta-Cell Regeneration in Type 1-diabetes Patients

The main goal of this study is to find a reasonably safe and tolerable treatment for adult patients with type 1-diabetes and that regain some of the endogenous insulin secretion, improve the patients' quality of life (QoL) and reduce the risk of both short- and long-term complications. The hypothesis tested is that oral GABA treatment with the newly developed compound Remygen will be safe and induce regain of some endogenous insulin secretion in adult patients with type 1-diabetes diagnosis for more than five years. The first part of the study will include 6 patients and be performed as a Safety and Dose Escalation study in three steps. The main study is a three-arm, open label, single center, clinical trial. Eligible patients will be randomized into one of three active treatment arms to receive oral GABA treatment for 6 months.

Inclusion Criteria:

1. Informed consent given by patients according to national regulations

2. Type 1 diabetes diagnosed ≥ 5 years at the time of screening

3. Must have been diagnosed with Type 1-diabetes before the age of 25

4. Age ≥18 and ≤50

5. Fasting c-peptide levels should be in the range from not detectable levels up to <0.12 nmol/L

6. For males of childbearing potential adequate contraception is as follows:

   1. condom (male)

   2. abstinence from heterosexual intercourse

   3. 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:

1. Females of child-bearing potential
2. Previous or current treatment with immunosuppressant therapy (although topical and inhalation steroids are accepted)
3. Treatment with any oral or injected anti-diabetic medications other than insulin
4. Patients on medications which may disturb GABA action, such as Baclofen, Valium, Acamprosate, Neurontin, or Lyrica
5. HbA1c > 90 mmol/mol
6. eGFR <60 ml/min
7. 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).
8. Known cancer disease
9. Known sleeping apnea or pulmonary disorder with carbon dioxide rentention in blood
10. Previous history of pancreatitis or other exocrine pancreatic disorder
11. A history of epilepsy, myasthenia gravis, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles
12. A history of alcohol or drug abuse
13. A significant illness other than diabetes within 2 weeks prior to first dosing
14. Known human immunodeficiency virus (HIV) or hepatitis
15. Females who are breastfeeding
16. Males not willing to use adequate contraception during the study period.
17. Known hypersensitivity agains benzodiazepins or any excipients of study drugs
18. Participation in other clinical trials with a new chemical entity within 3 months or 5 half-lives of the new chemical entity, whatever longest.
19. Inability or unwillingness to comply with the provisions of this protocol
20. 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.