Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes, TA-7284
Brief summary
The purpose of this study is to evaluate the safety, pharmacokinetics and pharmacodynamics of TA-7284 orally administered once daily for 15 days (1 day followed by a 1 day washout period and then 14 consecutive days). Dose escalation design is utilized in this study, and dose escalation of TA-7284 will be starting with 25 mg (step 1). Subsequent doses of 100 mg (step 2), 200 mg (step 3) and 400 mg (step 4) are planned after review of the tolerance and PK of the previous step.
Interventions
DRUGTA-7284
Patients will receive single ascending dose of TA-7284 in each step (4 doses planned: 25, 100, 200 and 400 mg), once daily, 15 days (1 day followed by a 1 day washout period and then 14 consecutive days)
DRUGPlacebo of TA-7284
Patients will receive placebo tablets in each step, once daily, 15 days (1 day followed by a 1 day washout period and then 14 consecutive days)
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Clinically stable Type 2 Diabetes Mellitus * Females without childbearing potential * Body mass index (BMI) \>= 18.5 kg/m2 and \<= 39.9 kg/m2 * Hemoglobin A1c levels \>= 6.5% and \<= 10% * Fasting blood glucose levels \>= 140 mg/dL and \<= 270 mg/dL * Systolic blood pressure \>= 95 mmHg and \<= 160 mmHg, and diastolic blood pressure \>= 50 mmHg and \<= 100 mmHg, and pulse rate \>= 50 bpm * Patients who have not been administered anti-diabetic medication within 2 weeks Prior to dosing * Medicines if necessary for Hypertension or Dyslipidemia should be administered with stable dosage at least 3 months * Treatment with diet and exercise should be unchanged for more than 3 months
Exclusion criteria
* Type 1 Diabetes Mellitus or Secondary Diabetic Mellitus * History of diabetic complications which need treatment * Treatment with insulin, thiazolidinediones, thiazide diuretics、beta blockers or systemic steroids within 3 months prior to informed consent * Serum creatinine \> upper limit of the normal range * Patients with significant complications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Adverse Events, Adverse Drug Reactions | 19 days | In the safety analysis population, adverse events incidences and adverse drug reactions incidences were calculated by dose. |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics- 1)Plasma Concentration of TA-7284: Tmax,Cmax, AUC, Etc.; and 2)Urinary Excretion of TA-7284: Ae, Ae%, CLr | 19 days |
| Pharmacodynamics- 1)Urinary Glucose Excretion; 2)Plasma Glucose Concentration; 3)Insulin Concentration in Serum; 4)Insulinogenic Index;and 5)Hemoglobin A1c and Glycoalbumin | 18 days |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TA-7284 25 mg TA-7284 25 mg was administered as a single dose, followed by a one-day washout, and multiple doses for 14 days. | 12 |
| TA-7284 100 mg TA-7284 100 mg was administered as a single dose, followed by a one-day washout, and multiple doses for 14 days. | 12 |
| TA-7284 200 mg TA-7284 200 mg was administered as a single dose, followed by a one-day washout, and multiple doses for 14 days. | 14 |
| TA-7284 400 mg TA-7284 400 mg was administered as a single dose, followed by a one-day washout, and multiple doses for 14 days. | 13 |
| Placebo Placebo was administered as a single dose, followed by a one-day washout, and multiple doses for 14 days. | 10 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | TA-7284 25 mg | TA-7284 100 mg | TA-7284 200 mg | TA-7284 400 mg | Placebo |
|---|---|---|---|---|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 8.8 | 49 years STANDARD_DEVIATION 10.6 | 52.1 years STANDARD_DEVIATION 7.6 | 56.2 years STANDARD_DEVIATION 8.6 | 56.5 years STANDARD_DEVIATION 8.2 | 57.6 years STANDARD_DEVIATION 6.3 |
| Sex: Female, Male Female | 11 Participants | 4 Participants | 0 Participants | 1 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 50 Participants | 8 Participants | 12 Participants | 13 Participants | 9 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 12 | 8 / 12 | 5 / 14 | 6 / 13 | 8 / 10 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 14 | 0 / 13 | 0 / 10 |
Outcome results
Primary
Safety: Adverse Events, Adverse Drug Reactions
In the safety analysis population, adverse events incidences and adverse drug reactions incidences were calculated by dose.
Time frame: 19 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TA-7284 25 mg | Safety: Adverse Events, Adverse Drug Reactions | Adverse events | 75.0 percentage of incidences |
| TA-7284 25 mg | Safety: Adverse Events, Adverse Drug Reactions | Adverse drug reactions | 50.0 percentage of incidences |
| TA-7284 100 mg | Safety: Adverse Events, Adverse Drug Reactions | Adverse events | 66.7 percentage of incidences |
| TA-7284 100 mg | Safety: Adverse Events, Adverse Drug Reactions | Adverse drug reactions | 16.7 percentage of incidences |
| TA-7284 200 mg | Safety: Adverse Events, Adverse Drug Reactions | Adverse events | 35.7 percentage of incidences |
| TA-7284 200 mg | Safety: Adverse Events, Adverse Drug Reactions | Adverse drug reactions | 7.1 percentage of incidences |
| TA-7284 400 mg | Safety: Adverse Events, Adverse Drug Reactions | Adverse drug reactions | 7.7 percentage of incidences |
| TA-7284 400 mg | Safety: Adverse Events, Adverse Drug Reactions | Adverse events | 46.2 percentage of incidences |
| Placebo | Safety: Adverse Events, Adverse Drug Reactions | Adverse events | 80.0 percentage of incidences |
| Placebo | Safety: Adverse Events, Adverse Drug Reactions | Adverse drug reactions | 30.0 percentage of incidences |
Secondary
Pharmacodynamics- 1)Urinary Glucose Excretion; 2)Plasma Glucose Concentration; 3)Insulin Concentration in Serum; 4)Insulinogenic Index;and 5)Hemoglobin A1c and Glycoalbumin
Time frame: 18 days
Secondary
Pharmacokinetics- 1)Plasma Concentration of TA-7284: Tmax,Cmax, AUC, Etc.; and 2)Urinary Excretion of TA-7284: Ae, Ae%, CLr
Time frame: 19 days