Absorption, Metabolism, Distribution, and Excretion of Letermovir.

Background: Letermovir is approved for prophylaxis of cytomegalovirus infection and disease in cytomegalovirus-seropositive hematopoietic stem-cell transplant (HSCT) recipients.

Objective: HSCT recipients are required to take many drugs concomitantly. The pharmacokinetics, absorption, distribution, metabolism, and excretion of letermovir and its potential to inhibit metabolizing enzymes and transporters in vitro were investigated to inform on the potential for drug-drug interactions (DDIs).

Making Better Dose Decisions: Using Exposure-Response Modeling to Integrate Efficacy Outcome of Two Phase IIb Clinical Trials of Ubrogepant for Migraine Treatment.

Ubrogepant (MK-1602) is a novel, oral, calcitonin gene-related peptide receptor antagonist in clinical development with positive phase III outcomes for acute treatment of migraine. This paper describes the population exposure-response (E-R) modeling and simulations, which were used to inform the phase III dose-selection rationale, based on ~ 800 participants pooled across two phase IIb randomized dose-finding clinical trials. The E-R model describes the placebo and ubrogepant treatment effects based on migraine pain end points (2-hour pain relief and 2-hour pain freedom) at various dose levels.

Leveraging Digital Health Technologies and Outpatient Sampling in Clinical Drug Development: A Phase I Exploratory Study.

Merck & Co, Inc (Kenilworth, NJ) is investing in approaches to enrich clinical trial data and augment decision making through use of digital health technologies, outpatient sampling, and real-time data access. As part of this strategy, a phase I study was conducted to explore a few technologies of interest. In this fixed-sequence two-period trial, 16 healthy subjects were administered 50-mg once-daily sitagliptin packaged in a bottle that electronically captured the date and time study medication was dispensed (period 1) and in a traditional pharmacy bottle (period 2).

Harnessing the Potential of Emerging Digital Health and Biological Sampling Technologies for Clinical Drug Development: Promise to Reality.

Advances in emerging innovative technologies have led to optimistic outlooks on their transformative potential for healthcare and clinical trials. Given the increased attention, this white paper by the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) presents perspectives on pharmaceutical and biotechnology industry trends for innovative digital health, adherence, and outpatient sampling technologies. As stimulus for cross-company scientific dialog points to consider for adoption, implementation, and recommendations to broaden uptake are proposed.