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ADAPTIVE DESIGN IN CLINICAL DEVELOPMENT OF NEXT-IN-CLASS DRUGS

Introduction: The next-in-class drugs are the original drugs that by chemical structure and mode of action similar to their predecessors of the same pharmacological group. The clinical development of the next-in-class drugs usually follows the same path as for innovative drugs including all phases. Since the effects of the next-in-class drugs can be predicted with certain accuracy, there is a potential for optimizing their clinical program in terms of duration and costs. Adaptive design represents the innovative approach that allows for efficiency and acceleration of drug development.

Objectives: The study objective was to assess the perspectives of the adaptive design methods in clinical development of the next-in-class drugs of different pharmacological groups including hypoglycemic agents, anticoagulants and anti-HIV drugs.

Methods: The adaptive designs were developed and implemented in phase II-III studies of three next-in-class drugs. The seamless two-stage design was used for sequential assessment of two dosing schemes of gosogliptin (DPP-4 inhibitor), as well as for the dose selection and its further efficacy and safety assessment in phase II/III studies of tearxaban (factor Xa inhibitor) and elsulfavirine (NNRTI). The measures necessary to control a type I error and avoid biases were assumed at all stages.

Results and discussion: In three conducted trials the non-inferiority of the next-in-class drugs to the standards of care was demonstrated as well as comparative or improved safety profiles. The adaptive designs allowed for combining two trials/phases in one study providing efficient use of resources and expedited market access.

Conclusion: The adaptive design can be successfully implemented in clinical programs of next-in-class drugs.

Иллюстрации

Fig. 1. HbA1c change at Week 12 for monotherapy

Fig. 2. HbA1c change at Week 36 for combination therapy

Fig. 3. Risk/benefit analysis for tearxaban dose selection at Stage 1

Fig. 4. Efficacy and safety analysis of tearxaban 100 mg and enoxaparin at Stage 2

Fig. 5. Risk/benefit analysis for elsulfavirine dose selection at Stage 1

Fig. 6. Efficacy and safety of elsulfavirine 20 mg and efavirenz at Stage 2

Fig. 7.  Seamless design for two treatment regimens

Fig. 8. Seamless phase II/III design

Table 1 Comparative analysis of clinical trial designs

DOI: 10.18413/2313-8971-2017-3-3-121-134
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