Phase 2
Completed N=70
A Study Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2330672 Administered With Metformin to Type 2 Diabetes Patients
Source: ClinicalTrials.gov NCT02202161 ↗Enrolled (actual)
70
Serious AEs
1.6%
Results posted
Nov 2017
Primary outcomePrimary: Change From Baseline in Derived Plasma Glucose Parameter Over a 24-hour Period-fasting and Weighted Mean Glucose Area Under Curve (AUC[0-24 Hour]) — -6.58; -8.25; -1.40; -38.56 Mg/deciliter
Summary
This study is being conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK2330672 compared to sitagliptin when administered with metformin for 14 days to subjects with type 2 diabetes mellitus (T2DM). Approximately 72 male and female subjects aged 30-64 years with T2DM and currently taking metformin will be recruited for this study. Eligible subjects will begin a run-in period of 13-15 days to stabilize on metformin 850 milligram (mg) twice a day (BID). Subjects will then be randomized to GSK2330672 10 mg, 20 mg, 30 mg, 90 mg, matching placebo or open-label sitagliptin 50 mg for 14 days BID. Subjects will return for a follow-up visit 7-10 days after discharge.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Derived Plasma Glucose Parameter Over a 24-hour Period-fasting and Weighted Mean Glucose Area Under Curve (AUC[0-24 Hour]) |
-6.58; -8.25; -1.40; -38.56; -34.38; -24.78 | — |
| PRIMARY Number of Participants With Incidence and Nature of Adverse Events (AEs) and Serious Adverse Events (SAEs) |
9; 4; 5; 5; 8; 8 | — |
| PRIMARY Number of Participants With Abnormal Hematology With Potential Clinical Concern (PCI) |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Number of Participants With Abnormal Clinical Chemistry With PCI |
1; 0; 2; 2; 2; 1 | — |
| PRIMARY Number of Participants With Abnormal Urinalysis Data |
0; 1; 0; 0; 0; 0 | — |
| PRIMARY Summary of Urinalysis Data-mean Specific Gravity |
1.0193; 1.0182; 1.0128; 1.0190; 1.0172; 1.0189 | — |
| PRIMARY Summary of Urinalysis Data-mean pH |
5.73; 6.00; 6.10; 6.11; 5.83; 5.95 | — |
| PRIMARY Number of Participants With Abnormal Electrocardiogram (ECG) Findings Any Time Post-Baseline |
9; 4; 4; 8; 6; 6 | — |
| PRIMARY Change From Baseline in Vital Signs Assessments-temperature |
-0.133; -0.280; 0.040; 0.033; 0.033; 0.010 | — |
| PRIMARY Change From Baseline in Vital Signs Assessments-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
-0.083; -1.600; -6.600; -1.556; -4.111; -2.700 | — |
| PRIMARY Change From Baseline in Vital Signs Assessments-heart Rate |
-0.500; 9.200; 4.400; 0.556; 4.667; 1.400 | — |
| PRIMARY Number of Bowel Movements (Stool Frequency) as Rated Using the Bristol Stool Form Scale (BSFS) Across Days 1 to 14 |
15.2; 28.2; 38.4; 35.0; 37.3; 35.9 | — |
| PRIMARY Number of Events With the Rating on Quality of Stools as Rated Using the BSFS Across Days 1 to 14 |
2; 1; 1; 2; 6; 2 | — |
| PRIMARY Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) |
0; 0; 2; 2; 0; 0 | — |
| PRIMARY Number of Participants With Fecal Occult Blood Monitoring for Symptomatic or Visible Gastrointestinal Bleeding or Asymptomatic Occult Bleeding |
0; 1; 1; 0; 0; 1 | — |
| SECONDARY PK Parameters for Metformin Steady State PK Parameters When Co-dosed With GSK2330672, Sitagliptin or Placebo-maximum Observed Concentration (Cmax) |
1102.2; 1289.3; 1219.9; 1160.0; 1378.8; 1376.6 | — |
| SECONDARY PK Parameters for Metformin Steady State PK Parameters When Co-dosed With GSK2330672, Sitagliptin or Placebo-time of Occurrence of Cmax (Tmax) |
1.510; 1.000; 1.000; 1.050; 1.750; 1.500 | — |
| SECONDARY PK Parameters for Metformin Steady State PK Parameters When Co-dosed With GSK2330672, Sitagliptin or Placebo-area Under the Concentration-time Curve Over the Dosing Interval of 10 Hours (AUC[0-10]) |
6805.8; 5982.0; 7066.2; 7066.5; 8090.5; 8375.3 | — |
| SECONDARY Ratio to Baseline in Fasting Low-density Cholesterol (LDL) Cholesterol, High-density Cholesterol (HDL) Cholesterol, Total Cholesterol, Non-HDL Cholesterol and Triglycerides |
0.95; 0.99; 0.84; 0.84; 0.74; 0.80 | — |
| SECONDARY Ratio to Baseline in Fasting Apolipoprotein B |
0.97; 0.95; 0.78; 0.81; 0.69; 0.76 | — |
| SECONDARY Sitagliptin Steady State PK Parameters When Co-dosed With Metformin-Cmax Following the First and Second Sitagliptin Doses |
238.2; 188.5 | — |
| SECONDARY Sitagliptin Steady State PK Parameters When Co-dosed With Metformin-Tmax Following the First and Second Sitagliptin Doses |
2.000; 3.050 | — |
| SECONDARY Sitagliptin Steady State PK Parameters When Co-dosed With Metformin-AUC(0-10) |
1473.5 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female between 30 and 64 years of age inclusive, at the time of signing the informed consent
- Subjects with a diagnosis of T2DM for at least 3 months prior to screening, taking metformin for at least 4 weeks prior to screening, taking a metformin daily dose of>= 1000 mg and having an Glycosolated haemoglobin A1c (HbA1c) value of 7-11% inclusive at screening. The investigator should make an effort to obtain documentation of medical history or prescription of metformin to substantiate the diagnosis of T2DM
- Fasting plasma glucose = 80 milliliter per minute (mL/min) using the modification of diet in renal disease (MDRD) equation or chronic kidney disease epidemiology collaboration (CKD-EPI) formula in the study procedures manual (SPM); No conditions which make hypoxia, dehydration, or sepsis likely; No cardiac disease (including no history of myocardial infarction, stroke, hospitalization for acute coronary syndrome, or heart failure)
- Body mass index (BMI) within the range 24 - 40 kilogram per meter square (kg/m^2) (inclusive)
- Other than T2DM, subjects should be in good general health with (in the opinion of the investigator) no clinically significant and relevant abnormalities of medical history or physical examination that would introduce additional risk factors or interfere with study procedures or objectives, based on a medical evaluation including medical history, physical examination, vital signs, and laboratory tests
- A female subject is eligible to participate if she is of non-childbearing potential defined as: Pre-menopausal females with a documented tubal ligation, bilateral oophorectomy, or hysterectomy [for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]; OR Postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 million international units (MlU)/mL and estradiol 160 millimeters of mercury (mmHg) or diastolic pressure >90 mmHg on a single assessment. If systolic pressure >140 mmHg or diastolic pressure >90 mmHg, a single repeat is allowed within 1 hour. Subjects whose blood pressure is well-controlled by taking anti-hypertensive medications (e.g., beta blockers, angiotensin converting enzyme(ACE) inhibitors, angiotensin II receptor antagonists, calcium channel blockers, and thiazide diuretics) are permitted
- History of untreated pernicious anemia or who have laboratory parameters suggestive of subclinical megaloblastic anemia (e.g., increased mean corpuscular volume [MCV] with low red blood cells [RBC] count and/or haemoglobin [Hb] level).
- Thyroid disease: Uncorrected Thyroid Dysfunction as Fasting plasma thyroid stimulating hormone (TSH) outside of the normal range, as determined at the screening visit. Subjects on stable thyroid replacement therapy and with TSH in the normal range are eligible if approved by the GSK Medical Monitor. Unevaluated thyroid nodule or goiter at screening
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram (g) of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits
- History of sensitivity to heparin or heparin-induced thrombocytopenia
- History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy (including other Dipeptidyl Peptidase-IV [DPP-IV] inhibitors) that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation
- Current or relevant previous significant medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any co
Data sourced from ClinicalTrials.gov (NCT02202161). 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.