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Use of Prohibited Medication, a Potentially Overlooked Confounder in Clinical Trials: Omarigliptin (Once-weekly DPP-4 Inhibitor) Monotherapy Trial in 18- to 45-year-olds
- Source :
- Clinical therapeutics. 39(10)
- Publication Year :
- 2017
-
Abstract
- Purpose The objective of this clinical trial was to assess the efficacy and safety of omarigliptin monotherapy in young adult patients with type 2 diabetes mellitus (T2DM). Unexpected efficacy results in this trial led to a series of investigations that identified the use of prohibited medication by a substantial number of trial patients. Methods Patients with T2DM who were ≥18 to Findings The mean age of trial participants was 39.2 years, approximately 60% were male, mean body mass index was 32.5 kg/m2, and mean duration of diabetes was 3.1 years. The mean baseline HbA1c value was 7.9% in the omarigliptin group and 8.1% in the placebo group. After 24 weeks, the least squares mean change (95% CI) in HbA1c value from baseline was –0.33% (–0.60 to –0.06) in the omarigliptin group and –0.45% (–0.72 to –0.18) in the placebo group, with a between-group difference of 0.12% (–0.26 to 0.49; P = 0.535). Similarly, no between-group difference was observed for the other glycemic parameters (2-hour postmeal glucose and fasting plasma glucose levels). No issues were identified in drug allocation, dispensing or supply, patient compliance with trial medication, sample handling or analysis, or site trial conduct that explained the observed results. Measurement of drug levels from future biomedical research samples uncovered the use, with no investigator knowledge, of an antihyperglycemic agent that was prohibited by the protocol (ie, metformin) by 42.4% (39 of 92) of patients. Metformin was used by more patients in the placebo group (57% [25 of 44]) than in the omarigliptin group (29% [14 of 48]). Implications The use of prohibited metformin in a trial of a dipeptidyl peptidase–4 inhibitor, omarigliptin, introduced a confounding factor that invalidated the results of the trial. This behavior may have been encouraged in the trial by protocol-specified self-monitoring of blood glucose levels. Use of prohibited medication may be an underappreciated confounder in clinical trial research. Trial registrations: MK-3102-028 (US); ClinicalTrials.gov identifier, NCT01814748; EudraCT number, 2012-004303-12 (EU).
- Subjects :
- Adult
Blood Glucose
Male
medicine.medical_specialty
Adolescent
030209 endocrinology & metabolism
Pharmacology
Heterocyclic Compounds, 2-Ring
Body Mass Index
Medication Adherence
03 medical and health sciences
Young Adult
0302 clinical medicine
Double-Blind Method
Diabetes mellitus
Internal medicine
medicine
Humans
Pharmacology (medical)
030212 general & internal medicine
Young adult
Glycemic
Pyrans
Glycated Hemoglobin
Dipeptidyl-Peptidase IV Inhibitors
business.industry
Confounding
Type 2 Diabetes Mellitus
Confounding Factors, Epidemiologic
Middle Aged
medicine.disease
Metformin
Clinical trial
Diabetes Mellitus, Type 2
Drug Therapy, Combination
Female
business
Body mass index
medicine.drug
Subjects
Details
- ISSN :
- 1879114X
- Volume :
- 39
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Clinical therapeutics
- Accession number :
- edsair.doi.dedup.....b5efd6deedd29b6c4d3702bb731c01bc