Phase 3
Completed N=936
30 Week Parallel Group Comparison Study of Linagliptin + Pioglitazone (5+15, 5+30 and 5+45 mg) qd Versus Respective Monotherapies, Followed by a Comparison of 5mg+30mg and 5mg+45mg Versus Respective Monotherapies in Type 2 Diabetes for up to 54 Weeks
Source: ClinicalTrials.gov NCT01183013 ↗Enrolled (actual)
936
Serious AEs
7.0%
Results posted
Apr 2014
Primary outcomePrimary: Change From Baseline in HbA1c After 30 Weeks of Treatment. — -0.66; -0.69; -0.87; -0.39 percent — p=0.1571
Summary
The primary objective is to demonstrate superior glycaemic control (HbA1c reduction) after 30 weeks of linagliptin/pioglitazone (5/15, 5/30 and 5/45 mg) versus the respective individual monotherapies of pioglitazone (15 mg, 30 mg, or 45 mg, administered orally once daily), and linagliptin (5 mg, administered orally once daily). In addition, durability of treatment effect and safety under chronic treatment conditions will be investigated.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in HbA1c After 30 Weeks of Treatment. |
-0.66; -0.69; -0.87; -0.39; -0.83; -1.06 | 0.1571 |
| SECONDARY Occurrence of Cumulative Treat to Target Efficacy Response, of HbA1c Under Treatment of < 7.0% After 30 Weeks of Treatment |
39; 55; 68; 29; 45; 61 | 0.4639 |
| SECONDARY Occurrence of Cumulative Treat to Target Efficacy Response, of HbA1c Under Treatment of < 6.5% After 30 Weeks of Treatment |
20; 28; 39; 14; 24; 38 | 0.7359 |
| SECONDARY Occurrence of Relative Efficacy Response (HbA1c Lowering by at Least 0.5% After 30 Weeks of Treatment) |
79; 83; 90; 54; 79; 91 | 0.7540 |
| SECONDARY HbA1c Change From Baseline by Visit Over Time |
-0.22; -0.16; -0.20; -0.23; -0.43; -0.47 | — |
| SECONDARY Fasting Plasma Glucose (FPG) Change From Baseline After 30 Weeks of Treatment |
-15.16; -25.49; -28.69; -1.46; -18.84; -27.33 | 0.4275 |
| SECONDARY Fasting Plasma Glucose (FPG) Change From Baseline by Visit Over Time |
-14.43; -16.38; -15.72; -4.25; -19.25; -26.89 | — |
| SECONDARY Two-hour Postprandial Glucose (2hPPG) Change From Baseline at Week 30 by Meal Tolerance Test (MTT) |
-30.65; -83.00; -82.98; -51.61; -67.26; -87.94 | 0.0057 sig |
| SECONDARY Time to First Use of Rescue Therapy |
0.8117; 0.8533; 0.9051; 0.7756; 0.8854; 0.9078 | — |
| SECONDARY Incidence of Rescue Therapy During the First 30 Weeks of Treatment |
20; 17; 11; 26; 12; 10 | 0.3052 |
Eligibility Criteria
Inclusion criteria
- Diagnosis of type 2 diabetes mellitus prior to informed consent
- Male and female patients with insufficient glycaemic control (HbA1c >= 7.0 to = 18 and 240 mg/dl (> 13.3 mmol/l) after an overnight fast during screening or placebo run-in period (cf. Section 3.3.4.1)
- Myocardial infarction within 6 months, stroke or TIA within 3 months prior to informed consent
- Clinical evidence of active liver disease (e.g. jaundice) or the ALT level > 2.5 times the upper limit of normal (according to pioglitazone label)
- Bariatric surgery, performed within the past 2 years prior to informed consent or planned at the time of informed consent
- Gastrointestinal surgeries prior to informed consent that induce chronic malabsorption
- Known hypersensitivity or allergy to the investigational products (linagliptin and/or pioglitazone) or their excipients (including matching placebos)
- Contraindications to pioglitazone as defined in the local prescribing information (SPC), particularly :
- Diagnose of heart failure or history of heart failure
- Haemodialysis patients, due to limited experience with pioglitazone
- Treatment with gemfibrozil, montelukast, trimethoprim, or rifampicin - according to pioglitazone label and respective restrictions in Section 4.2.2
- Treatment with rosiglitazone, pioglitazone, GLP-1 analogues, or insulin within 3 months prior to informed consent
- Treatment with anti-obesity drugs (e.g. sibutramine, orlistat) 3 months prior to informed consent
- Alcohol or drug abuse within the 3 months prior to informed consent or history of alcoholism
- Current treatment with systemic corticosteroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent
- Participation in another trial with an investigational drug within 30 days prior to informed consent
- Any other clinical condition as judged by the investigator that would not allow the safe completion of the protocol, e.g. inability of patients to comply with study procedures
- Pre-menopausal women (last menstruation <= 1 year prior to informed consent) who:
- are nursing or pregnant or
- are of child-bearing potential (i.e. not permanently sterilised) and are not practicing a highly effective method of birth control, or do not plan to continue using this method throughout the study and do not agree to submit to periodic pregnancy testing during participation in the trial.
A highly effective method of birth control is defined - according to the Note for Guidance on non-clinical safety studies for the conduct of human trials for pharmaceuticals (CPMP/ICH/286/95, modification) - as those which result in a low failure rate (i. e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices/systems (IUDs/IUSs), sexual abstinence or vasectomised partner
- Symptomatic gallbladder disease in the last six months
- Medical history of pancreatitis.
- Patients with urinary bladder cancer or a history of urinary bladder cancer or uninvestigated macroscopic haematuria
- Any other contraindication or restriction for use of pioglitazone in accordance with the local prescribing information for pioglitazone.
Data sourced from ClinicalTrials.gov (NCT01183013). 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.