RP-008 in Combination With Daily Oral Varenicline for the Treatment of Trigeminal Neuralgia

The goal of this study is to evaluate if KRIYA-748 (RP-008) is safe, tolerable, and preliminary effective in treating trigeminal neuralgia (TN) when used in combination with varenicline tartrate. The study will also assess what doses of RP-008 are safe and tolerable for participants and how the severity of participants' TN pain and frequency of facial pain attacks are affected.

Inclusion Criteria: * Participant is capable of providing signed informed consent. * Participant must be between 18 to 80 years of age (inclusive), at the time of signing the informed consent. * Confirmed diagnosis of classical or idiopathic TN according to the criteria of the International Classification of Headache Disorders-3rd edition (ICHD-3, 2018). * The diagnosis of TN established at least 6 months prior to Screening. * Participant has purely unilateral pain attacks limited primarily to the maxillary (V2) and/or mandibular (V3) division of the trigeminal nerve. * Participant has failed at least 1 standard of care anti-epileptic agent (e.g., carbamazepine, oxcarbazepine, pregabalin, gabapentin, phenytoin, lamotrigine). Failure to a prior anti-epileptic medication is defined as insufficient pain relief despite use of a therapeutic dose for an adequate duration of time or being unsuitable due to contraindications or intolerance to side effects. * Participant is on stable dosage of any TN anti-epileptic agent(s) for a minimum of 6 weeks prior to Screening. Exclusion Criteria: * Participant has bilateral TN pain attacks. * Participants with secondary TN, defined by ICHD-3 as TN caused by an underlying disease (e.g., tumor in the cerebellopontine angle, arteriovenous malformation, or multiple sclerosis). * Participants with facial pain not meeting the ICHD-3 diagnostic criteria for either classical or idiopathic TN, including: trigeminal autonomic cephalalgias, cluster headache, hemicrania continua, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). * Participants who had no change in pain after taking sodium channel blockers despite the use of a therapeutic dose for an adequate duration of time.