[PMC free article] [PubMed] [Google Scholar] 23
[PMC free article] [PubMed] [Google Scholar] 23. apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer. Upon request, and subject to certain criteria, conditions and exceptions (see https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information), Pfizer will provide access to individual de\identified participant data from Pfizer\sponsored global interventional clinical studies conducted for medicines, vaccines and medical devices (1) for indications that have been approved in the United States and/or European Union, or (2) in programmes that have been terminated (i.e. development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data may be requested from Pfizer trials 24?months after study completion. The de\identified participant data will be made available to researchers Gramicidin whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure Gramicidin portal. To gain access, data requestors must enter into a data access agreement with Pfizer. Abstract Aim To evaluate the long\term efficacy and safety of ertugliflozin in adults with type 2 diabetes mellitus inadequately controlled on metformin. Materials and Methods A Gramicidin 104\week Phase III, randomized double\blind study with a 26\week placebo\controlled period (Phase A) and a 78\week period (Phase B) where blinded glimepiride was added to non\rescued placebo participants with fasting fingerstick glucose 6.1?mmol/L. Results through week 104 are reported. Results Mean (standard error) change in HbA1c from baseline was ?0.7% (0.07) and ?1.0% (0.07) at week 52; ?0.6% (0.08) and ?0.9% (0.08) at week 104 for ertugliflozin 5 and 15?mg. At week 52, 34.8% and 36.6% participants had HbA1c 7.0%, and 24.6% and 33.7% at week 104, for ertugliflozin 5 and 15?mg. Ertugliflozin reduced fasting plasma glucose (FPG), body weight and systolic blood pressure (SBP) from baseline through week 104. The incidence of female genital mycotic infections (GMIs) was higher with ertugliflozin, and symptomatic hypoglycaemia was lower for ertugliflozin versus placebo/glimepiride. Minimal bone mineral density (BMD) changes were observed, similar to placebo/glimepiride, except at total hip where reduction in BMD was greater with ertugliflozin 15?mg versus placebo/glimepiride: difference in least squares means (95% CI) C0.50% (?0.95, ?0.04) at week 52 and ?0.84% (?1.44, ?0.24) at week 104. Conclusions Ertugliflozin maintained improvements from baseline in HbA1c, FPG, body weight and SBP through week 104. Ertugliflozin was well tolerated, with non\clinically relevant changes in BMD. Compared with placebo/glimepiride, ertugliflozin increased female GMIs, but reduced the incidence of symptomatic hypoglycaemia. ClinicalTrials.gov Identifier: “type”:”clinical-trial”,”attrs”:”text”:”NCT02033889″,”term_id”:”NCT02033889″NCT02033889. =?0.009 for both ertugliflozin Gramicidin groups versus placebo/glimepiride. d =?0.017 for ertugliflozin 5?mg versus placebo/glimepiride; =?0.003 for ertugliflozin 15?mg versus placebo/glimepiride. 3.3.2. Prespecified AEs of special interest The incidence of symptomatic hypoglycaemia was lower in the ertugliflozin 5?mg and 15?mg groups (5.8% and 5.9%, respectively) than in the placebo/glimepiride group (13.4%) (0.009 for both ertugliflozin doses). The incidence of documented hypoglycaemia was 21.1%, 13.5% and 14.1% for placebo/glimepiride, ertugliflozin 5?mg and ertugliflozin 15?mg, respectively. There were no cases of severe hypoglycaemia. The incidence of GMIs was higher in the ertugliflozin groups compared with the placebo/glimepiride group for female participants (0.017 for ertugliflozin 5?mg; 0.003 for ertugliflozin 15?mg). One female participant in the ertugliflozin 5?mg group discontinued study medication because of a GMI AE (vulvovaginal mycotic infection). None of the GMI events was serious, all were mild or moderate in Gramicidin intensity. The incidence of UTIs was INSL4 antibody not notably different among the 3 treatment groups. The incidence of hypovolemia was low and similar across groups; all hypovolemia events were mild or moderate in intensity (Table ?(Table11). 3.3.3. Adjudicated AEs There were fewer confirmed fractures in both ertugliflozin groups than in the placebo/glimepiride group: ertugliflozin 5?mg, 3 fractures in 3 participants (1 high and 2 low trauma); ertugliflozin 15?mg, 2 fractures in 2 participants (both low trauma); placebo/glimepiride, 10 fractures in 7 participants (1 high and 9 low trauma). One participant in the ertugliflozin 15?mg group experienced a serious AE of diabetic ketoacidosis that met the charter case definition of certain to be ketoacidosis; the participant had suspected type 1 diabetes (possible Latent Autoimmune Diabetes of Adulthood). Three participants (1 in the ertugliflozin 5?mg group and 2 in the placebo/glimepiride group) had an AE of acute pancreatitis adjudicated as mild acute pancreatitis; none was considered to be caused by the study medication. One participant in the ertugliflozin 15?mg group had 1 renal event that was adjudicated as possibly related to study medication. One participant in the placebo/glimepiride group had an AE of liver injury that was adjudicated as possibly related to study medication. Results of adjudication for cardiovascular events in this study will be analysed in a programme\wide manner across ertugliflozin clinical.