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Diabetic Ketoacidosis and Related Events in the Canagliflozin Type 2 Diabetes Clinical Program. Diabetes Care 2015;38:1680-1686

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Abstract

We thank Dr. Dhatariya (1) for his interest in our study that assessed the incidence of serious adverse events of diabetic ketoacidosis (DKA) and related events in the canagliflozin type 2 diabetes clinical trial program (2). Our analysis of DKA and related events was based on a standard collection of adverse event reports from investigators and included verbatim terms that map to the specific terms of diabetic ketoacidosis, ketoacidosis, metabolic acidosis, and acidosis from the Medical Dictionary …
RESPONSE TO COMMENT ON ERONDU ET AL.
Diabetic Ketoacidosis and Related Events
in the Canagliflozin Type 2 Diabetes
Clinical Program. Diabetes Care
2015;38:16801686
Diabetes Care 2016;39:e19 |DOI: 10.2337/dci15-0026
We thank Dr. Dhatariya (1) for his inter-
est in our study that assessed the inci-
dence of serious adverse events of
diabetic ketoacidosis (DKA) and related
events in the canagliozin type 2 diabe-
tes clinical trial program (2). Our analysi s
of DKA and related events was based
on a standard collection of adverse
event reports from investigators and in-
cluded verbatim terms that map to the
specic terms of diabetic ketoacidosis,
ketoacidosis, metabolic acidosis, and
acidosis from the Medical Dictionary
for Regulatory Activities (MedDRA).
These methods are in line with the U.S.
Food and Drug Administration guidelines
on good pharmacovigilance practices,
which require investigators to report any
adverse event (3). We acknowledge
that the amount of data included in
case reports of adverse events may
vary; however, all available details were
included in the published post hoc anal-
ysis. The data included in the article
came from a pooling of studies con-
ducted in more than 50 countries glob-
ally, where access to source data and
details contained in the source vary
considerably. Occasionally, information
was not available for a variety of reasons
(e.g., inability of the investigator to obtain
detailed source documents from the in-
stitution where the patient was hospital-
ized or the patient not providing medical
release of information). Further prospec-
tive studies are needed to better under-
stand the risk of DKA in patients with
type 2 diabetes treated with canagliozin.
Dhatariya (1) also raises concerns re-
garding access to primary clinical trial
data. Janssen Research & Development,
LLC (the sponsor of canagliozin), is com-
mitted to clinical trial data transparency in
order to advance science and medicine
and has an agreement with the Yale Uni-
versity Open Data Access (YODA) Project.
Under the agreement, YODA serves as an
independent body to review and make -
nal decisions on requests from physicians
and investigators to access clinical study
reports and anonymized participant-level
data from completed studies (4).
Funding and Duality of Interest. This work
was sponsored by Janssen Research &
Development , LLC. Editorial support was pro-
vided by Kimberly Fuller, PhD, of MedErgy,
andwasfundedbyJanssenGlobalServices,
LLC. Canagliozin was developed by Janssen Re-
search & Development, LLC, in collaboration
with Mitsubishi Tanabe Pharma Corporation.
N.E., M.D., K.W., and G.M. are full-time em-
ployees of Janssen Research & Development,
LLC. No other potential conicts of interest rele-
vant to this article were reported.
References
1. Dhatariya K. Comment on Erondu et al. Diabetic
ketoacidosis and related events in the canagliozin
type 2 diabetes clinical program. Diabetes Care
2015;38:16801686 (Letter). Diabetes Care 2016;
39:e18. DOI: 10.2337/dc15-1956
2. Erondu N, Desai M, Ways K, Meininger G.
Diabetic ketoacidosis and related events in the
canagliozin type 2 diabetes clinical program.
Diabetes Care 2015;38:16801686
3. U.S. Department of Health and Human Servic es,
Food and Drug Administration, Center for Drug
Evaluation and Research, Center for Biologics
Evaluation and Research (CBER). Guidance for in-
dustry: good pharmacovigilance practices and
pharmacoepidemiologic assessment [Internet],
2005. Available from http://www.fda.gov/
downloads/RegulatoryInformation/Guidances/
UCM126834.pdf. Accessed 12 October 2015
4. Yale Universit y. The YODA Project [Inter net],
2015. Available from http://yoda.yale.edu/.
Accessed 12 October 2015
Janssen Research & Development, LLC, Raritan, NJ
Corresponding author: Gary Meininger, gmeining@its.jnj.com.
© 2016 by the American Diabe tes Association. Readers may use this article as long as the work is properly cited, t he use is educational and not for prot,
and the work is not altered.
Ngozi Erondu, Mehul Desai, Kirk Ways,
and Gary Meininger
Diabetes Care Volume 39, January 2016 e19
e-LETTERS COMMENTS AND RE SPONSES
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Article
Full-text available
I read with interest the article by Erondu et al. (1) on the Janssen Research & Development, LLC, experience of diabetic ketoacidosis (DKA) in a canagliflozin series of studies. They reported the characteristics of 12 cases of DKA in their cohort of 17,596 patients in their studies. However, there remain some potentially troubling issues. In their report, they described 4 out of the 12 patients as having DKA, but they did not report the patients’ pH, bicarbonate, anion gap, or ketone measurements (and in one of the …
Article
Full-text available
This study assessed the incidence of serious adverse events of diabetic ketoacidosis (DKA) among patients with type 2 diabetes treated with canagliflozin. All serious adverse events of DKA and related events (ketoacidosis, metabolic acidosis, and acidosis) from 17,596 patients from randomized studies of canagliflozin through 11 May 2015 were analyzed. Serious adverse events of DKA and related events were reported in 12 patients (0.07%), including 4 (0.07%), 6 (0.11%), and 2 (0.03%) treated with canagliflozin 100 and 300 mg and comparator, respectively; corresponding incidence rates were 0.522, 0.763, and 0.238 per 1,000 patient-years, respectively. Most patients with DKA and related events had a blood glucose >300 mg/dL (16.7 mmol/L) at presentation of DKA, were on insulin, and had DKA-precipitating factors, including some with type 1 diabetes/latent autoimmune diabetes of adulthood. DKA and related events occurred at a low frequency in the canagliflozin type 2 diabetes program, with an incidence consistent with limited existing observational data in the general population with type 2 diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program
  • K Dhatariya
  • Comment On Erondu
Dhatariya K. Comment on Erondu et al. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care 2015;38:1680-1686 (Letter). Diabetes Care 2016; 39:e18. DOI: 10.2337/dc15-1956
Comment on Erondu et al. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care 2015;38:1680–1686 (Letter)
  • Dhatariya