Research Article: Randomized clinical trial comparing efficacy and safety of brand versus generic alendronate (Bonmax®) for osteoporosis treatment

Date Published: July 5, 2017

Publisher: Public Library of Science

Author(s): Aasis Unnanuntana, Atthakorn Jarusriwanna, Panupan Songcharoen, Tuan Van Nguyen.

http://doi.org/10.1371/journal.pone.0180325

Abstract

Although the same efficacy and tolerability are anticipated due to both drugs containing the same active ingredients, comparative studies between brand and generic alendronate are limited. Accordingly, the objective of this study was to compare efficacy and safety between brand alendronate and a recently introduced generic alendronate drug.

A total of 140 postmenopausal women or men aged older than 50 years who met the indications for osteoporosis treatment were randomized to receive either generic (Bonmax®) or brand alendronate (Fosamax®) 70 mg/week over a 12-month period during the May 2014 to June 2015 study period. Endpoints included bone mineral density (BMD) changes at the lumbar spine, total hip, and femoral neck; percentage of patients with predefined levels of change in total hip and lumbar spine BMD at 12 months; and, changes in biochemical bone markers at 3, 6, and 12 months. Tolerability was evaluated by patient self-reporting of adverse experiences.

At 12 months post-treatment, BMD significantly increased at all sites in both groups. There were no differences in BMD percentage changes or the number of patients with stable or increased BMD after 1 year between groups. No significant differences in the amount of biochemical bone marker reduction or incidence of adverse events were observed between groups.

Generic and brand alendronate produced similar gains in BMD and reduction in bone turnover markers. Both medicadoitions were also equally well-tolerated. Based on these findings, generic alendronate (Bonmax®) is a viable alternative to the original brand of alendronate.

ClinicalTrials.gov NCT02371252

Partial Text

Osteoporosis is a systemic disease characterized by compromised bone strength that predisposes individuals to increased risk of fracture [1]. Fragility fracture is associated with premature mortality [2] and substantial decrease in quality of life (QOL) [3]. Moreover, both short- and long-term care for patients with fragility fractures place an enormous economic burden on the health care system [4]. Due to high personal and societal costs of fragility fracture, prevention is critically important. Once an individual has been identified as being at high risk for fracture, such as those diagnosed with osteoporosis or those with a history of fragility fracture, an appropriate pharmacological intervention should be employed.

This study was a 12-month randomized controlled, non-inferiority trial conducted at Siriraj Hospital, Mahidol University. The protocol and consent forms used were approved by the Siriraj Institutional Review Board (SIRB), Faculty of Medicine Siriraj Hospital, Mahidol University on 22 April 2014. This study was registered at ClinicalTrials.gov via the Protocol Registration and Results System (PRS) (NCT02371252) on 7 September 2014. The 4–5 month delay in protocol registration was due to time needed for translation of the protocol from Thai language to English language (S1 and S2 Files). A detailed informed consent form was signed by each participating patient, and all patient information was kept confidential. The study design and reporting format were based on CONSORT (Consolidated Standards of Reporting Trials) principles (S1 Checklist). The authors confirm that all ongoing and related trials for this drug/intervention are registered.

A total of 153 patients were screened during the study period. Of 153 patients, 13 patients were excluded from the study, as follows: 2 patients for declining to participate, 2 patients with severe dyspepsia, 2 patients with estimated glomerular filtration rate <35 mL/min/1.73 m2, 2 patients currently using bisphosphonate, and 5 patients had history of taking glucocorticoids during the past 6 months. The remaining 140 patients were enrolled. Included participants were randomized and allocated according to the study protocol (70 patients to the generic alendronate group and 70 patients to the brand alendronate group). Three patients died during study treatment as a result of underlying medical problems. Six patients were lost to follow-up during the study period. Nineteen patients discontinued medication after the randomization process for a variety of reasons that included fracture, severe side effects, and active medical condition. One hundred and twelve patients (80%) completed the study with data available for analysis at the end of the 12-month follow-up (Fig 1). In general, generic drugs contain active pharmaceutical ingredients similar to those used in original brand name drugs; therefore, preclinical studies and clinical trials on animals and patients to prove the safety and efficacy of generic drug products are not required [11,22]. Alternatively, bioequivalence studies are required that demonstrate safety and efficacy comparability between the generic and its brand predecessor [11]. Although therapeutically equivalent products are expected to have the same safety and efficacy profiles, many generic drugs are not administered under the same conditions [12]. In Thailand, many generic forms of alendronate are available. Various preparations of alendronate 70 mg per week contain different ratios of alendronate monosodium and alendronate sodium trihydrate. Changes in these content ratios may cause differences in pharmacokinetics and pharmacodynamics, which may result in different outcomes regarding efficacy and side effects. Most of these generic drugs provide comparative bioequivalence data with the original drug, but none has been compared in terms of therapeutic equivalence or safety/tolerability to brand alendronate.   Source: http://doi.org/10.1371/journal.pone.0180325

 

0 0 vote
Article Rating
Subscribe
Notify of
guest
0 Comments
Inline Feedbacks
View all comments