Teneligliptin and “Thorough QTc study”: thorough enough?
Department of Endocrinology, Nightingale Hospital, Kolkata, India
I read with interest the “Thorough QTc study” with teneligliptin by Erande et al.1 It came as a surprise to me that the basic structure required to conduct such a trial as per the ICH E14 recommendations for the industry was not followed.2 The recommended design to conduct such a trial was not universally followed (Table1).
View the original paper by Erande and colleagues
I read with interest the “Thorough QTc study” with teneligliptin by Erande et al1. It came as a surprise to me that the basic structure required to conduct such a trial as per the ICH E14 recommendations for the industry was not followed.2 The recommended design to conduct such a trial was not universally followed (Table1).
Table 1 Requirements for a thorough QT/QTc study2
The original thorough QT/QTc study was conducted by the recommending authority (PMDA) in Japan using a dose range of 40 mg (therapeutic dose) and 160 mg (experimental dose) for teneligliptin compared to moxifloxacin 400 mg (active control dose).3 The upper limit of 90% CI was more than 10 ms for the 160 mg dose in both sexes. More than 10 ms CI was also documented in females with the 40 mg dose, prompting the Japanese authorities to include this adverse event as a warning.
In view of the above-mentioned deficiency in the study design as well as reporting strategy, the data analyzed in the Erande et al, study can be considered as an effect of teneligliptin on QT interval and not a thorough QTc study.
I would be obliged if the following issues were adequately clarified with your involvement.
The author has no conflicts of interest to declare in this communication.
1. Erande S, Sarwardekar S, Desai B. QT/QTc safety and efficacy evaluation of teneligliptin in Indian type 2 diabetes mellitus patients: the “thorough QT/QTc” study (Q-SET study). Diabetes Metab Syndr Obes. 2019;12:961–967. doi:10.2147/DMSO.S202458
2. Guidance for Industry. E14 clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. [Online] Available from: https://www.fda.gov/media/71372/download.
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