DCB-DM101 in Healthy Volunteers and for Type 2 Diabetes Mellitus Patients

An Open-label Phase I Study to Assess the Safety and Tolerability Profile of Three Escalating Doses of DCB-DM101 in Healthy Volunteers and Optimum Dose of DCB-DM101 as add-on Treatment in Type 2 Diabetes Mellitus (T2DM) Patients

An Open-Label Phase I Study to Assess the Safety and Tolerability Profile of Three Escalating Doses of DCB-DM101 in Healthy Volunteers and Optimum Dose of DCB-DM101 as Add-on Treatment in Type 2 Diabetes Mellitus (T2DM) Patients

This is a single center, open-label, phase-I study consisting of two stages: Stage 1 will be dose-escalation study to assess the safety and tolerability profile of three escalating doses of DCB-DM101 in healthy volunteers and Stage 2 will apply optimum dose of DCB-DM101 as add-on treatment in T2DM patients. In Stage 2, patients are allowed to receive metformin for T2DM for routine use of which the dosing regimen should not be adjusted. No other medication/treatments for T2DM are allowed. Stage 2 can only be proceeded upon the approval of health authority in Taiwan. After determining the optimal dose for Stage 2, the reasons for determining such dose together with relevant supporting data should be submitted to health authority in Taiwan for review and to determine whether stage 2 can be proceeded and which dose should be employed for stage 2.

Inclusion Criteria:

Stage 1

1. Adult, male or female aged between 20-40 years old;
2. Physically and mentally healthy subjects as confirmed by an interview, medical history, clinical examination, chest X-rays, and electrocardiogram;
3. Body Mass Index (BMI) between 18.5 and 24, inclusive, (BMI will be calculated as weight in kilogram [kg]/height in meters2 [m2]);
4. Clinically normal hematology, biochemistry and urinalysis determinations based on investigator's discretion;
5. Subject is willing and able to comply with study procedures and sign informed consent.

Stage 2

1. Male or female aged between 20-70 years old;
2. Diagnosed T2DM (WHO 1999 criteria);
3. Not effective in alleviating T2DM after monotherapy of metformin 1,500mg/day [or 1,000mg/day if unable to tolerate higher dose] for 3 months
4. HbA1c of 7.0 % to 9.0% (inclusive);
5. BMI of at most 35 kg/m2;
6. Subject is willing and able to comply with study procedures and sign informed consent

Exclusion Criteria:

Stage 1

1. Subjects who have a history or evidence of a medical condition that would expose them to an undue risk of a significant adverse event or interfere with the assessments of safety or pharmacodynamics variables during the course of the trial, including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, immune, neurological, musculoskeletal or hematological disease as determined by the clinical judgment of the investigator;
2. Subject has received any investigational agent within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug;
3. Subjects have taken or potentially take any prescription medication and/or over the-counter medication from within 1 week prior to the first dose of study drug to the end of study period;
4. Subject has alcohol, caffeine, grapefruit juice, or nicotine consumption within 24 hours prior to the administration of study drug;
5. Female subject of childbearing potential who: is lactating; or has positive urine pregnancy test at Visit 1; or refuses to adopt at least two forms of birth control (at least one of which must be a barrier method) during the study.

Stage 2

1. Known or suspected allergy to any ingredients of study product
2. Pregnant or lactating or premenopausal with childbearing potential but not taking at least two forms of birth control (at least one of which must be a barrier method) during the study.

Note: Acceptable forms include:

1. Established use of oral, injected or implanted hormonal methods of contraception.
2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).
3. Barrier methods of contraception: Condom OR Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. 3. Participated in another clinical trial and received an investigational drug within four weeks prior to the present trial
4. Impaired hepatic function defined as alanine aminotransferase (ALT), aspartate transaminase (AST) or alkaline phosphatase (ALP) at least 2.5 times upper referenced limit
5. Impaired renal function defined as serum-creatinine at least 1.3 mg/dL (at least 115 umol/L) for males and at least 1.2 mg/dL (at least 106 umol/L) for females
6. With any uncontrolled illness or a history of any illness judged by the investigator that entering the trial may be detrimental to the subject
7. Metformin contraindications according to the package insert
8. Current treatment with systemic corticosteroids.