Opicapone Pharmacokinetics and Effects on Catechol- O -Methyltransferase Activity and Levodopa Pharmacokinetics in Patients With Parkinson Disease Receiving Carbidopa/Levodopa.

Objectives: Levodopa (LD) administered with dopa decarboxylase inhibitor is predominantly metabolized in the periphery by catechol- O -methyltransferase (COMT) to 3- O -methyldopa (3-OMD). Catechol- O -methyltransferase inhibition can improve treatment outcomes by decreasing variability in circulating LD concentrations. Opicapone is a once-daily COMT inhibitor approved in the US adjunctive to carbidopa (CD)/LD in patients with Parkinson disease experiencing "OFF" episodes.

Pharmacokinetic and Pharmacologic Characterization of the Dihydrotetrabenazine Isomers of Deutetrabenazine and Valbenazine.

Valbenazine and deutetrabenazine are vesicular monoamine transporter 2 (VMAT2) inhibitors approved for tardive dyskinesia. The clinical activity of valbenazine is primarily attributed to its only dihydrotetrabenazine (HTBZ) metabolite, [+]-α-HTBZ. Deutetrabenazine is a deuterated form of tetrabenazine and is metabolized to four deuterated HTBZ metabolites: [+]-α-deuHTBZ, [+]-β-deuHTBZ, [-]-α-deuHTBZ, and [-]-β-deuHTBZ.

A long-term, open-label study of valbenazine for tardive dyskinesia.

Background: Individuals with tardive dyskinesia (TD) who completed a long-term study (KINECT 3 or KINECT 4) of valbenazine (40 or 80 mg/day, once-daily for up to 48 weeks followed by 4-week washout) were enrolled in a subsequent study (NCT02736955) that was primarily designed to further evaluate the long-term safety of valbenazine.

Methods: Participants were initiated at 40 mg/day (following prior valbenazine washout). At week 4, dosing was escalated to 80 mg/day based on tolerability and clinical assessment of TD; reduction to 40 mg/day was allowed for tolerability.

A Phase 3, 1-Year, Open-Label Trial of Valbenazine in Adults With Tardive Dyskinesia.

Purpose/background: Valbenazine is approved to treat tardive dyskinesia (TD) in adults. KINECT 4 (NCT02405091) was conducted to explore the long-term effects of once-daily valbenazine in patients with TD.

Methods/procedures: The study included a 48-week, open-label treatment period and 4-week washout.

Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials.

Introduction: Valbenazine is a novel vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia in adults.

Objective: Using data from double-blind, placebo-controlled trials, analyses were conducted to evaluate the cardiovascular effects of once-daily valbenazine in patients with a psychiatric disorder who developed tardive dyskinesia after exposure to a dopamine-blocking medication.

Methods: Data were pooled from three 6-week, double-blind, placebo-controlled trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), and KINECT 3 (NCT02274558).

The Effects of Valbenazine in Participants with Tardive Dyskinesia: Results of the 1-Year KINECT 3 Extension Study.

Background: Valbenazine, a highly selective vesicular monoamine transporter 2 inhibitor, is approved for the treatment of tardive dyskinesia. This is the first report of long-term effects in adults with tardive dyskinesia.

Methods: Participants with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or a mood disorder who completed the 6-week, double-blind, placebo-controlled period of KINECT 3 were eligible to enter the 42-week valbenazine extension (VE) period and subsequent 4-week washout period.

Single Dose and Repeat Once-Daily Dose Safety, Tolerability and Pharmacokinetics of Valbenazine in Healthy Male Subjects.

Valbenazine (VBZ) is a vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia. The safety, tolerability and pharmacokinetics of VBZ following single and repeat once-daily (QD) dosing were evaluated in 2 randomized, single-center, double-blind studies in healthy male subjects. In the first study, 2 cohorts of 8 subjects were administered single doses (SD) of placebo (PBO; N = 2/period) or VBZ (N = 6/period; 1, 2, 5, or 12.

KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia.

Objective: Tardive dyskinesia is a persistent movement disorder induced by dopamine receptor blockers, including antipsychotics. Valbenazine (NBI-98854) is a novel, highly selective vesicular monoamine transporter 2 inhibitor that demonstrated favorable efficacy and tolerability in the treatment of tardive dyskinesia in phase 2 studies. This phase 3 study further evaluated the efficacy, safety, and tolerability of valbenazine as a treatment for tardive dyskinesia.

NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study.

Background: Tardive dyskinesia is a persistent movement disorder induced by chronic neuroleptic exposure. NBI-98854 is a novel, highly selective, vesicular monoamine transporter 2 inhibitor. We present results of a randomized, 6-week, double-blind, placebo-controlled, dose-titration study evaluating the safety, tolerability, and efficacy of NBI-98854 for the treatment of tardive dyskinesia.

Elagolix, an oral GnRH antagonist, versus subcutaneous depot medroxyprogesterone acetate for the treatment of endometriosis: effects on bone mineral density.

This randomized double-blind study, with 24-week treatment and 24-week posttreatment periods, evaluated the effects of elagolix (150 mg every day, 75 mg twice a day) versus subcutaneous depot medroxyprogesterone acetate (DMPA-SC) on bone mineral density (BMD), in women with endometriosis-associated pain (n = 252). All treatments induced minimal mean changes from baseline in BMD at week 24 (elagolix 150 mg: -0.11%/-0.

Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study.

This Phase 2 study evaluated the safety and efficacy of elagolix for treating endometriosis-associated pain. A total of 155 women with laparoscopically confirmed endometriosis were randomized to placebo, elagolix 150 mg, or elagolix 250 mg once daily for 12 weeks. Placebo patients were rerandomized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12.

Elagolix, an Oral GnRH Antagonist for Endometriosis-Associated Pain: A Randomized Controlled Study.

Objective: The aim of this study was to estimate the efficacy of elagolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of endometriosis-associated pelvic pain.

Methods: This was a phase II, randomized, placebo-controlled parallel group study conducted at 37 US centers, consisting of an 8-week double-blind period followed by a 16-week open-label period. Patients were 137 women aged 18 to 49, with laparoscopically confirmed endometriosis and moderate to severe nonmenstrual pelvic pain and dysmenorrhea, who were administered elagolix 150 mg daily or placebo.

No effect of the altered peptide ligand NBI-6024 on beta-cell residual function and insulin needs in new-onset type 1 diabetes.

Objective: This randomized, four-arm, placebo-controlled, dose-ranging phase 2 trial was conducted to determine whether repeated subcutaneous injections of the altered peptide ligand, NBI-6024, designed to inhibit autoreactive T-cells, improves beta-cell function in patients with recently diagnosed type 1 diabetes.

Research Design And Methods: A total of 188 patients, aged 10-35 years, with recently diagnosed type 1 diabetes were randomly assigned for a treatment consisting of the subcutaneous administration of placebo or 1, 0.5, or 0.

Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix.

Context: Parenteral administration of peptide GnRH analogs is widely employed for treatment of endometriosis and fibroids and in assisted-reproductive therapy protocols. Elagolix is a novel, orally available nonpeptide GnRH antagonist.

Objective: Our objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single-dose and 7-d elagolix administration to healthy premenopausal women.

Suppression of serum luteinizing hormone in postmenopausal women by an orally administered nonpeptide antagonist of the gonadotropin-releasing hormone receptor (NBI-42902).

Context: Parenteral administration of peptide GnRH analogs is widely used in clinical practice for the suppression of pituitary gonadotropins. NBI-42902 is an orally available, high-affinity nonpeptide antagonist of the human GnRH receptor.

Objective: The objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropin secretion of NBI-42902 in postmenopausal women.