A Phase 1 Single- and Multiple-dose Escalation Study of VX‑993 in Healthy Adults
Research type
Research Study
Full title
A Phase 1, Randomized, Double-blind, Placebo-controlled, Single- and Multiple-dose Escalation Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of VX‑993 in Healthy Adults
IRAS ID
1006145
Contact name
Alexander Craft
Contact email
Sponsor organisation
Vertex Pharmaceuticals Incorporated
Eudract number
2022-002413-42
Clinicaltrials.gov Identifier
Research summary
Pain is one of the most common symptoms for which patients seek medical attention. Current treatment options for pain are limited by poor efficacy and high rates of adverse events (AEs), leaving many patients without adequate pain control. Nonsteroidal anti-inflammatory drugs (NSAIDs) pose a potentially serious risk of gastrointestinal toxicity with acute and chronic use, hematologic toxicity with acute use, and nephrotoxicity with chronic use. Opioids are significantly limited by safety and tolerability issues and have a high abuse liability. Opioid associated deaths have increased in frequency over the past 2 decades. Opioids were involved in more than 77,000 overdose deaths in the US in 2021 and in approximately 74% of fatal drug overdoses in the EU in 2020.Given the limited treatment options, combined with the risks and constrained utility of current treatments, the development of new analgesics with improved efficacy and safety profiles is vital for better pain management and patient health outcomes. Despite the need for new analgesics, clinical development has exhibited a considerable lack of recent progress and innovation of new medications to treat pain. Over the last decade, the majority of approved analgesic drugs either act on the opioid receptor system or are NSAIDs; few new molecular entity drugs for moderate to severe pain have been approved. The majority of research activity focuses on developing abuse deterrent reformulations of existing narcotic pain drugs, or combinations with NSAIDs. The resultant compounds do not have substantially improved efficacy or safety. Voltage-gated sodium channel 1.8 (NaV1.8) plays a critical role in pain signaling. Support for this assertion arises from (1) evaluation of the role NaV1.8 plays in normal physiology, (2) pathological states arising from mutations in the NaV1.8 gene (SCN10A), and (3) pharmacology of known NaV1.8-modulating agents.
REC name
London - Surrey Borders Research Ethics Committee
REC reference
22/LO/0729
Date of REC Opinion
2 Dec 2022
REC opinion
Further Information Favourable Opinion