Phase 1
Completed N=48
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Doses of BI 10773 Tablets
Source: ClinicalTrials.gov NCT01924767 ↗Enrolled (actual)
48
Serious AEs
0.0%
Results posted
Jul 2014
Primary outcomePrimary: Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests — 0.0; 0.0; 0.0; 0.0 percentage of participants
Summary
To investigate safety, tolerability, pharmacokinetics and pharmacodynamics of BI 10773 with repeat dosing for eight days and the exploration of the pharmacokinetics and pharmacodynamics of BI 10773 after multiple dosing, including dose proportionality and assessment of steady state.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Clinically Relevant Findings in Physical Examination, Vital Signs and Clinical Laboratory Tests |
0.0; 0.0; 0.0; 0.0; 0.0; 8.3 | — |
| PRIMARY Percentage of Participants With Clinically Relevant Findings in Electrocardiogram (ECG) Results |
0.0; 0.0; 0.0; 0.0; 0.0; 100.0 | — |
| PRIMARY Micturition Frequency |
4.1; 2.6; 5.0; 3.9; 4.4; 0.3 | — |
| PRIMARY Assessment of Tolerability by Investigator |
91.7; 100.0; 100.0; 100.0; 100.0; 0.0 | — |
| SECONDARY Concentration of the Analyte in Plasma |
61.3; 240; 592; 2670; 66.6; 272 | — |
| SECONDARY Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval (AUC) |
468; 1890; 4780; 23300; 397; 1620 | — |
| SECONDARY Time to Maximum Concentration of the Analyte in Plasma |
1.50; 1.50; 1.50; 3.00; 1.50; 1.50 | — |
| SECONDARY Terminal Rate Constant in Plasma |
0.0618; 0.0586; 0.0654; 0.0527; 0.0686; 0.0491 | — |
| SECONDARY Half-life and Mean Residence Time of the Analyte in Plasma |
11.2; 11.8; 10.6; 13.2; 10.1; 14.1 | — |
| SECONDARY Apparent Volume of Distribution During the Terminal Phase |
192; 200; 177; 181; 176; 225 | — |
| SECONDARY Amount of Analyte Eliminated in Urine |
706; 2570; 5250; 18500; 941; 4530 | — |
| SECONDARY Fraction of Analyte Excreted Unchanged in Urine |
8.50; 8.43; 6.30; 6.17; 10.6; 14.7 | — |
| SECONDARY Apparent and Renal Clearance of the Analyte in Plasma |
198; 195; 193; 159; 201; 184 | — |
| SECONDARY Peak Trough Fluctuation |
323; 294; 281; 265 | — |
| SECONDARY Linearity Index |
0.983; 1.05; 1.02; 0.962 | — |
| SECONDARY Accumulation Ratios |
1.09; 1.13; 1.05; 0.972; 1.16; 1.23 | — |
| SECONDARY Change From Baseline to Day 8 in Urinary Glucose Excretion |
-3254.43; 34638.37; 78709.87; 74030.40; 88040.32 | 0.0067 sig |
| SECONDARY Mean Daily Glucose |
-13.85; -27.03; -34.04; -25.89; -30.96 | 0.0449 sig |
| SECONDARY Fasting Plasma Glucose |
-15.88; -21.01; -25.69; -14.21; -24.85 | 0.2239 |
| SECONDARY Serum Insulin |
38.1; 55.2; 51.2; 40.2; 35.2; 45.4 | — |
Eligibility Criteria
Inclusion criteria
- Male and postmenopausal or hysterectomised female patients with proven diagnosis of type 2 diabetes mellitus treated with diet and exercise only or on a maximum of two oral antidiabetic agents except thiazolidindiones with at least one agent taken at 50% of its maximum dose or less.
- Glycosylated haemoglobin A1 (HbA1c) £ 8.5 % at screening.
- Age >21 and Age 60 and Age 18.5 and 240 mg/dl (>13.3 mmol/L) on two consecutive days during washout.
- Glycosylated haemoglobin A1 (HbA1c) >8.5% at screening
- Clinically relevant concomitant diseases other than type 2 diabetes, hyperlipidaemia and medically treated hypertension, such as:
- Any late stage complication of diabetes (e.g. retinopathy, polyneuropathy, vegetative disorders, diabetic foot)
- Renal insufficiency (calculated creatinine clearance 160/95mmHg (measured at training visit and each of the timepoints of Day -1), stroke and TIA (Transistoric ischaemic attack)
- Neurological disorders (such as epilepsy) or psychiatric disorders
- Acute or relevant chronic infections (e.g. HIV, repeated urogenital infections)
- Any gastrointestinal, hepatic, respiratory, endocrine or immunological disorder
- History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
- A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)
- A history of additional risk factors for TdP (torsade des pointes) (e.g., heart failure, hypokalemia, family history of sudden death before the age of 50)
Data sourced from ClinicalTrials.gov (NCT01924767). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.