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Novel design for a phase IIa placebo-controlled, double-blind randomized withdrawal study to evaluate the safety and efficacy of CNV1014802 in patients with trigeminal neuralgia.

ABSTRACT: BACKGROUND:Trigeminal neuralgia (TN) is a rare severe unilateral facial pain condition. Current guidelines in trigeminal neuralgia management recommend sodium channel blockers--carbamazepine or oxcarbazepine--as the first-line treatment. However, the currently available drugs are often associated with poor tolerability resulting in sub-optimal pain control. CNV1014802 is a novel sodium channel blocker that is being assessed in the treatment of trigeminal neuralgia. Due to the severity of the condition, it is not ethical to conduct a traditional placebo-controlled randomized controlled trial. It is also difficult to use an active control such as carbamazepine, the current gold standard, because of its complex pharmacology and potential for drug interactions. METHODS/DESIGN:The trial uses a randomized withdrawal design to assess efficacy in this rare condition. There is a 21-day open-label phase followed by a randomized 28-day placebo-controlled phase for responders. Thirty patients will be randomized. The primary outcome measure will be pain relief, but secondary measures of quality of life will be of significant importance given the effect of this condition on activities of daily living. Safety and adverse event endpoints are described. DISCUSSION:There have been very few well-controlled, randomized, placebo-controlled studies in trigeminal neuralgia, and the majority of drugs have had other primary uses. Due to the severity of the pain, minimizing the time a patient is administered placebo was a key factor in designing this study. This study will not only provide data on the efficacy of CNV1014802 in trigeminal neuralgia, but will also provide information on the effectiveness and acceptability of a novel trial design in trigeminal neuralgia. TRIAL REGISTRATION:Trial number NCT01540630.

SUBMITTER: Zakrzewska JM

PROVIDER: S-EPMC4222641 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Novel design for a phase IIa placebo-controlled, double-blind randomized withdrawal study to evaluate the safety and efficacy of CNV1014802 in patients with trigeminal neuralgia.

Zakrzewska Joanna M JM Palmer Joanne J Ettlin Dominik A DA Obermann Mark M Giblin Gerard M P GM Morisset Valerie V Tate Simon S Gunn Kevin K

Trials 20131123

<h4>Background</h4>Trigeminal neuralgia (TN) is a rare severe unilateral facial pain condition. Current guidelines in trigeminal neuralgia management recommend sodium channel blockers--carbamazepine or oxcarbazepine--as the first-line treatment. However, the currently available drugs are often associated with poor tolerability resulting in sub-optimal pain control. CNV1014802 is a novel sodium channel blocker that is being assessed in the treatment of trigeminal neuralgia. Due to the severity of ...[more]

PMID: 24267010

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Project description:BackgroundTrigeminal neuralgia (TN) is a debilitating pain disorder that still lacks an ideal treatment option. Pulsed radiofrequency (PRF), especially with high output voltage, is a novel and minimally invasive technique. PRF is regarded a promising treatment option for TN patients who respond poorly to medical treatment; however, the available evidence still lacks high quality randomized controlled trials (RCTs). Our study aimed to evaluate the long-term (1 year and 2 years) effects and safety of high-voltage PRF in primary TN patients and provide stronger evidence for TN treatment options.MethodsWe performed a multicenter, double-blind, RCT in adults (aged 18-75 years) with primary TN who responded poorly to drug therapy or were unable to tolerate the side effects of drug. Eligible participants were randomly assigned (1:1) to receive either high voltage PRF or nerve block with steroid and local anesthetic drugs. The primary endpoint was the 1-year response rate. This trial has been registered in the clinicaltrials.gov website (registration number: NCT03131466).ResultsOne hundred and sixty-two patients were screened for enrollment between April 28th,2017 and September1st, 2019, among whom, 28 were excluded. One hundred and thirty-four participants were randomly assigned to either receive high voltage PRF (n = 67) or nerve block (n = 67). The proportion of patients with a positive response at 1-year after the procedure in the PRF group was significantly higher than that in the nerve block group in the intention-to-treat population (73.1% vs. 32.8%, p < 0.001). There was no difference between groups in the incidence of adverse events.ConclusionsOur findings support that high voltage PRF could be a preferred interventional choice prior to receiving more invasive surgical treatment or neuro-destructive treatment for TN patients who have poor responses to medical treatment.Trial registrationOur study has been registered at ClinicalTrials.gov (trial registration number: NCT03131466).

Project description:Abstract Endogenous Cushing’s syndrome (CS) is a rare, serious disorder caused by chronically elevated cortisol. A phase 3, open-label study (SONICS) of levoketoconazole in adults with CS and mean urinary free cortisol (mUFC) ≥1.5 × upper limit of normal (ULN) at baseline demonstrated normalization of mUFC in 62% of those completing 6 months of maintenance treatment (Fleseriu M, et al. Lancet Diabetes Endocrinol. 2019;7[11]:855-865). LOGICS is an ongoing, phase 3, double-blind, placebo-controlled, randomized-withdrawal study further investigating the safety and efficacy of levoketoconazole in patients who completed the SONICS study, or patients with CS who are levoketoconazole treatment-naive (ClinicalTrials.gov identifier: NCT03277690). The primary objective of LOGICS is to evaluate the effect of withdrawing levoketoconazole treatment to placebo, versus continuing treatment with levoketoconazole, on the cortisol therapeutic response established during open-label levoketoconazole therapy. The study includes (1) a screening phase (up to 13 weeks to allow for washout of CS medications); (2) a dose titration-maintenance phase (150-600 mg BID [dosed as needed to target mUFC normalization]) of ≥14 weeks, with at least the final 4 weeks demonstrating mUFC normalization prior to advancing to the randomized-withdrawal (R-W) phase; (3) a double-blind, placebo-controlled R-W phase (levoketoconazole or placebo; up to 8 weeks); and (4) a double-blind restoration phase (levoketoconazole and placebo; 8 weeks). Patients are randomized 1:1 in the R-W phase to continue their therapeutic dose of levoketoconazole, established during the dose titration-maintenance phase, or to receive an equivalent number of placebo tablets. Up to ~54 subjects are targeted for randomization. The primary efficacy endpoint, assessed at the completion of R-W phase, is the proportion of patients with loss of therapeutic response to levoketoconazole (mUFC ≥1.5x ULN, >40% above baseline if baseline value is >ULN [SONIC-completer cohort only], or early rescue criterion met) upon withdrawing to placebo, compared with continuing treatment with levoketoconazole, during the R-W phase. Secondary endpoints include changes from baseline to all postbaseline visits in R-W phase for mUFC, late-night salivary cortisol, CS cardiovascular biomarkers (fasting glucose, fasting insulin, hemoglobin A1c, homeostatic model assessment-insulin resistance, total and LDL cholesterol, high-sensitivity C-reactive protein), CS clinical signs and symptoms (acne, hirsutism [women only], and peripheral edema scores), and patient-reported outcomes of QoL (Cushing QoL questionnaire score) and depression (Beck Depression Inventory II). Potential liver toxicity, QT prolongation, and adrenal insufficiency are prespecified adverse events of special interest.

Dataset Information

Novel design for a phase IIa placebo-controlled, double-blind randomized withdrawal study to evaluate the safety and efficacy of CNV1014802 in patients with trigeminal neuralgia.

Publications

Novel design for a phase IIa placebo-controlled, double-blind randomized withdrawal study to evaluate the safety and efficacy of CNV1014802 in patients with trigeminal neuralgia.

Similar Datasets

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