Dataset Information

Efficacy and safety of valbenazine in Japanese patients with tardive dyskinesia: A multicenter, randomized, double-blind, placebo-controlled study (J-KINECT).

ABSTRACT:

Aim

Valbenazine is approved in the US for treatment of tardive dyskinesia (TD); however, efficacy/safety data in Asian populations are lacking. We assessed the efficacy/safety of valbenazine in Japanese patients.

Methods

This phase II/III, multicenter, randomized, double-blind, placebo-controlled study (NCT03176771) included adult psychiatric patients with TD, who were randomly allocated to receive placebo or valbenazine (once-daily 40- or 80-mg) for a 6-week, double-blind period, after which the placebo group was switched to valbenazine for a 42-week extension. The primary endpoint was change from baseline in Abnormal Involuntary Movement Scale (AIMS) total score at Week 6; clinical global impression of improvement of TD (CGI-TD) was also assessed.

Results

Of 256 patients, 86, 85, and 85 were allocated to the 40-mg valbenazine, 80-mg valbenazine, and placebo groups, respectively. Least-squares mean (95% confidence interval) change from baseline in AIMS score at Week 6 was -2.3 (-3.0 to -1.7) in the valbenazine 40-mg group, -3.7 (-4.4 to -3.0) in the 80-mg group, and -0.1 (-0.8 to 0.5) in the placebo group; both treatment groups showed statistically significant improvements vs. placebo. Patients switched to valbenazine at Week 6 showed similar improvements in AIMS scores, which were maintained to Week 48. Improvements in CGI-TD scores were observed for both treatment groups vs. placebo. Incidence of adverse events was highest in the 80-mg group; common events included nasopharyngitis, somnolence, schizophrenia worsening, hypersalivation, insomnia, and tremor.

Conclusion

The efficacy/safety profile of valbenazine was similar to that of previous clinical trials, supporting its use for TD treatment in Japanese patients.

SUBMITTER: Horiguchi J

PROVIDER: S-EPMC9826124 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Efficacy and safety of valbenazine in Japanese patients with tardive dyskinesia: A multicenter, randomized, double-blind, placebo-controlled study (J-KINECT).

Horiguchi Jun J Watanabe Koichiro K Kondo Kazuoki K Iwatake Atsushi A Sakamoto Hajime H Susuta Yutaka Y Masui Hideaki H Watanabe Yumi Y

Psychiatry and clinical neurosciences 20220917 11

<h4>Aim</h4>Valbenazine is approved in the US for treatment of tardive dyskinesia (TD); however, efficacy/safety data in Asian populations are lacking. We assessed the efficacy/safety of valbenazine in Japanese patients.<h4>Methods</h4>This phase II/III, multicenter, randomized, double-blind, placebo-controlled study (NCT03176771) included adult psychiatric patients with TD, who were randomly allocated to receive placebo or valbenazine (once-daily 40- or 80-mg) for a 6-week, double-blind period, ...[more]

PMID: 36114799

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Project description:Abstract Background: Valbenazine is a novel and highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor that is being evaluated for the treatment of tardive dyskinesia (TD), a persistent movement disorder resulting from exposure to antipsychotics or other dopamine receptor blocking agents (DRBAs). The efficacy of valbenazine in treating TD was demonstrated in a Phase 3 clinical trial (KINECT 3; NCT02274558), which included subjects with underlying schizophrenia/schizoaffective disorder or mood disorder. Further analyses of data from that trial were conducted to explore the efficacy of valbenazine across diagnostic subgroups. Methods: Subjects in this 6-week, double-blind, placebo-controlled trial were randomized 1:1:1 to once-daily valbenazine 80 mg, valbenazine 40 mg, or placebo. The primary endpoint was change from baseline to Week 6 on the Abnormal Involuntary Movement Scale (AIMS) total score (items 1–7) for valbenazine 80 mg vs placebo in the intent-to-treat (ITT) population. AIMs were videotaped and ratings were conducted by central raters blind to study visit and group. Additional outcomes included AIMS total score change (40 mg vs placebo) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI TD) score (80 and 40 mg vs placebo) at Week 6. In addition to being evaluated in the ITT population, these outcomes were analyzed in subgroups categorized by underlying psychiatric diagnosis (schizophrenia/schizoaffective disorder or mood disorder). Results: At Week 6 in the ITT population (N = 225), AIMS score improvement was significantly greater with valbenazine 80 mg than placebo (least squares [LS] mean change from baseline: 80 mg, 3.2; placebo, −0.1; P < .0001). AIMS score change at Week 6 for valbenazine 40 mg (1.9) was also greater than placebo (P = .0021). Statistical testing was not conducted in the subgroups, but the magnitude of AIMS improvement in these patients was comparable to results in the overall ITT population: schizophrenia/schizoaffective disorder (n = 148; mean change from baseline: 80 mg, −3.1; 40 mg, −1.5; placebo, +0.4); mood disorder (n = 77; 80 mg, 3.6; 40 mg, −2.5; placebo, −0.7). CGI-TD scores at Week 6 in the ITT population indicated greater global improvement with valbenazine than placebo, but between-group differences were not statistically significant (LS mean scores: 80 mg, 2.9; 40 mg, 2.9; placebo, 3.2). CGI-TD outcomes in the subgroups were as follows: schizophrenia/schizoaffective disorder (mean scores: 80 mg, 3.0; 40 mg, 2.9; placebo, 3.1); mood disorder (80 mg, 2.7; 40 mg, 2.9; placebo, 3.2). Psychiatric status remained stable during the 6-week double-blind treatment period. Conclusion: Once-daily treatment with valbenazine improved TD regardless of underlying psychiatric diagnosis.

Project description:ObjectiveTo evaluate the effects of once-daily valbenazine (40 or 80 mg/d) in older and younger adults with tardive dyskinesia (TD).MethodsData were pooled from three 6-week, randomized, double-blind, placebo-controlled (DBPC) studies (KINECT [NCT01688037], KINECT 2 [NCT01733121], and KINECT 3 [NCT02274558]) and two long-term studies (KINECT 3 extension and KINECT 4 [NCT02405091]). Outcomes analyzed in older and younger participants (55 years or older and younger than 55 years, respectively) included Abnormal Involuntary Movement Scale (AIMS) response (threshold of greater than or equal to 50% improvement from baseline in total score [items 1 to 7]) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) response (score 2 or less ["very much improved" or "much improved"]). Safety assessments included treatment-emergent adverse events (TEAEs).ResultsAt week 6 (end of DBPC treatment), the percentage of participants who met the AIMS response threshold was higher with valbenazine versus placebo in both subgroups: 55 years or older (80 mg/d, 39.7% [P < .001]; 40 mg/d, 28.6% [P < .01]; placebo, 9.7%); younger than 55 years (80 mg/d, 39.5% [P < .001]; 40 mg/d, 20.0% [P > .05]; placebo, 10.8%). The percentage of participants with CGI-TD response was also higher with valbenazine versus placebo: 55 years or older (80 mg/d, 41.3% [P < .01]; 40 mg/d, 30.2% [P > .05]; placebo, 19.4%); younger than 55 years (80 mg/d, 39.5% [P < .05]; 40 mg/d, 35.3% [P < .05]; placebo, 18.5%). Responses at week 48 (end of long-term treatment, combined doses) were as follows: 55 years or older (AIMS, 70.7%; CGI-TD, 82.8%); younger than 55 years (AIMS, 58.7%; CGI-TD, 72.3%). No significant differences between older and younger subgroups were found for AIMS or CGI-TD response. No new safety signals or TEAEs of clinical concern were found in older participants who received long-term treatment.ConclusionsValbenazine improved TD and was generally well tolerated in older and younger adults.

Project description:Abstract Background: Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder resulting from exposure to dopamine receptor-blocking agents (DRBAs), such as antipsychotics. Valbenazine is a novel and highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor that is being evaluated for the treatment of TD and other movement disorders. Clinical studies include a Phase 3 trial of valbenazine in adults who had TD and underlying schizophrenia/schizoaffective disorder or mood disorder (KINECT 3; NCT02274558). The primary end point of this trial was met as demonstrated by a significant difference between valbenazine 80 mg/day and placebo for the Abnormal Involuntary Movement Scale (AIMS) dyskinesia total score (Items 1–7) change from baseline. Additional analyses of AIMS data from this trial were conducted to assess treatment response in subjects with TD. Methods: In this 6-week, double-blind, placebo-controlled trial, subjects were randomized 1:1:1 to once-daily treatment with valbenazine 80 mg, valbenazine 40 mg, or placebo. Treatment response was defined as ≥50% reduction in the AIMS total score. AIMS responders were analyzed by study visit (Weeks 2, 4, and 6) in the intent-to-treat (ITT) population and in subgroups categorized by underlying psychiatric diagnosis (schizophrenia/schizoaffective disorder or mood disorder). Numbers needed to treat (NNTs) were calculated for AIMS responders (valbenazine vs placebo) at Week 6. Significance testing was not conducted in the subgroups. Results: At Week 6 in the ITT population (N = 225), AIMS responder rates were significantly higher with valbenazine than with placebo: 80 mg, 40.0% (P < .0001; NNT = 4); 40 mg, 23.8% (P = .0200; NNT=7); placebo, 8.7%. Treatment with valbenazine 80 mg versus placebo also resulted in significantly higher responder rates at Week 2 (23.4% vs 5.3%, P = .0016) and Week 4 (28.8% vs 9.7%, P = 0.0039). Subjects treated with valbenazine 40 mg also had higher response rates at Week 2 (14.3% vs 5.3%) and Week 4 (15.6% vs 9.7%) relative to placebo-treated subjects, but the differences were not statistically significant. In subjects with schizophrenia/schizoaffective disorder (n = 148) or mood disorder (n = 77), AIMS responder rates were higher with valbenazine than placebo at all study visits. The highest responder rates were found at Week 6 and similar in the schizophrenia subgroup (80 mg, 40.9%, NNT = 4; 40 mg, 26.2%, NNT = 6; placebo, 9.3%) and mood subgroup (80 mg, 38.5%, NNT = 4; 40 mg, 19.0%, NNT=9; placebo, 7.7%). Conclusion: These study results, based on a rigorous definition of treatment response, indicate that substantial TD improvements occurred more frequently with valbenazine than placebo in adults diagnosed with schizophrenia/schizoaffective disorder or mood disorder. A significant difference between the 80-mg dose and placebo for the AIMS response was observed as early as 2 weeks of treatment.

Project description:IntroductionValbenazine is a novel vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia in adults.ObjectiveUsing 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.MethodsData were pooled from three 6-week, double-blind, placebo-controlled trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), and KINECT 3 (NCT02274558). Data from the 42-week valbenazine extension period of KINECT 3 were also analyzed. Outcomes of interest included cardiovascular-related treatment-emergent adverse events, vital sign measurements, and electrocardiogram parameters.ResultsThe pooled safety population included 400 participants (placebo, n = 178; valbenazine 40 mg/day, n = 110; valbenazine 80 mg/day, n = 112). A history of cardiac disorders was present in 11.8% of participants, and 74.3% were taking a concomitant medication with known potential for QT prolongation. Mean changes from baseline to week 6 in supine vital signs and QTcF (Fridericia correction) were as follows for placebo, valbenazine 40 mg/day, and valbenazine 80 mg/day, respectively: systolic blood pressure (0.2, - 2.1, - 1.8 mmHg), diastolic blood pressure (- 0.1, - 1.6, - 1.2 mmHg), heart rate (- 1.7, - 2.2, - 1.7 bpm), QTcF interval (1.2, 1.1, 2.1 ms); all p > 0.05 for valbenazine vs. placebo. No statistically significant differences were observed between placebo and valbenazine in cardiovascular-related, treatment-emergent adverse events. No notable additional effects on cardiovascular outcomes were found with up to 48 weeks of valbenazine treatment.ConclusionsResults from double-blind, placebo-controlled trials showed no apparent difference between valbenazine and placebo on cardiovascular outcomes. No additional cardiovascular risk was detected during a longer extension study with valbenazine.

Project description:ObjectiveTo evaluate the efficacy and safety of two dosing regimens of fremanezumab in Japanese and Korean patients with episodic migraine.BackgroundEpisodic migraine, which accounts for more than 90% of migraine cases, is inadequately addressed by widely available preventive therapies. Fremanezumab, a monoclonal antibody that selectively targets the trigeminal sensory neuropeptide calcitonin gene-related peptide involved in migraine pathogenesis, has demonstrated efficacy in international Phase 3 trials of patients with both chronic and episodic migraine.MethodsThis Phase 3 randomized, placebo-controlled trial randomly assigned patients with episodic migraine to receive subcutaneous fremanezumab monthly (225 mg at baseline, week 4, and week 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. The primary endpoint was the mean change from baseline in the monthly average number of migraine days during the 12-week treatment period after the first dose.ResultsOf 357 patients enrolled (safety set, n = 356; full analysis set, n = 354), the least-squares mean (±standard error) reductions in the average number of migraine days per month during 12 weeks were significantly greater with fremanezumab monthly (-4.0 ± 0.4, n = 121) and fremanezumab quarterly (-4.0 ± 0.4, n = 117) than with placebo (-1.0 ± 0.4, n = 116; p < 0.0001 for both comparisons). The proportion of patients reaching at least a 50% reduction in the monthly average number of migraine days during the 12-week period after initial administration was also significantly improved with fremanezumab (fremanezumab monthly, 41.3%; fremanezumab quarterly, 45.3%; placebo, 11.2%; p < 0.0001 for both comparisons) as were other secondary endpoints (p < 0.001 for all comparisons between fremanezumab and placebo). Injection-site reactions were more common in fremanezumab-treated patients (fremanezumab monthly, 25.6%; fremanezumab quarterly, 29.7%; placebo, 21.4%).ConclusionFremanezumab prevents episodic migraine in Japanese and Korean patients to a similar extent than in previously reported populations with no new safety concerns.

Project description:ObjectiveTo determine the efficacy and safety of fremanezumab administration in Japanese and Korean patients with chronic migraine (CM).BackgroundAvailable preventive treatments for CM are limited by various efficacy and safety issues. Fremanezumab, a monoclonal antibody that targets the calcitonin gene-related peptide pathway involved in migraine pathogenesis, has been shown to be effective and well tolerated in large-scale, international Phase 3 trials.MethodsRandomized, placebo-controlled trial of patients with CM who received subcutaneous fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. Primary endpoint was the mean change from baseline in the monthly (28-day) average number of headache days of at least moderate severity during the 12 weeks after the first dose.ResultsAmong 571 patients randomized (safety set, n = 569; full analysis set, n = 566), the least-squares mean (±standard error [SE]) reduction in the average number of headache days of at least moderate severity per month during 12 weeks was significantly greater with fremanezumab monthly (-4.1 ± 0.4) and fremanezumab quarterly (-4.1 ± 0.4) than with placebo (-2.4 ± 0.4). The difference from the placebo group in the mean change (95% confidence interval [CI]) was -1.7 days (-2.54, -0.80) for the fremanezumab monthly group and -1.7 days (-2.55, -0.82) for the fremanezumab quarterly group (p < 0.001 vs. placebo for both fremanezumab groups). The percentage of patients with a ≥50% reduction in the average number of headache days of at least moderate severity per month (response rate) was higher with fremanezumab monthly (29.0%) and fremanezumab quarterly (29.1%) than with placebo (13.2%) in addition to other improvements in secondary endpoints, including reduction of acute medication use (mean change from baseline during 12-week period ± SE: fremanezumab monthly, -3.7 ± 0.4; fremanezumab quarterly, -3.9 ± 0.4; placebo, -2.4 ± 0.4) and improvements in disability scores (mean change from baseline in six-item Headache Impact Test score at 4 weeks after third injection ± SE: fremanezumab monthly, -8.1 ± 0.7; fremanezumab quarterly, -8.0 ± 0.7; placebo, -6.5 ± 0.7). Fremanezumab was well tolerated with a similar incidence of adverse events including injection-site reactions as placebo (patients with at least one treatment-emergent adverse event: fremanezumab total, n = 232 [61.4%]; placebo, n = 118 [61.8%]).ConclusionFremanezumab effectively prevents CM in Japanese and Korean patients and was well tolerated. No safety signal was detected.

Dataset Information

Efficacy and safety of valbenazine in Japanese patients with tardive dyskinesia: A multicenter, randomized, double-blind, placebo-controlled study (J-KINECT).

Aim

Methods

Results

Conclusion

Publications

Efficacy and safety of valbenazine in Japanese patients with tardive dyskinesia: A multicenter, randomized, double-blind, placebo-controlled study (J-KINECT).

Similar Datasets

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