Safety profile in tardive dyskinesia
In clinical trials, INGREZZA was generally well tolerated across a broad range of adult tardive dyskinesia (TD) patients1,2
COMBINED SAFETY ACROSS 3 KEY STUDIES
Adverse reactions in 3 placebo-controlled studies of a 6-week treatment duration reported at ≥2% and >placebo (safety population)1
| Adverse Reaction | INGREZZA (n=262) (%) |
Placebo (n=183) (%) |
|---|---|---|
| Somnolence | 10.9% | 4.2% |
| Anticholinergic effects | 5.4% | 4.9% |
| Balance disorders/fall | 4.1% | 2.2% |
| Headache | 3.4% | 2.7% |
| Akathisia | 2.7% | 0.5% |
| Vomiting | 2.6% | 0.6% |
| Nausea | 2.3% | 2.1% |
| Arthralgia | 2.3% | 0.5% |
Discontinuation due to side effects was 3% with INGREZZA® (valbenazine) capsules vs 2% with placebo1
Patients in the clinical trials were allowed to remain on their stable psychiatric treatment regimen1:
85%
took second-generation
antipsychotics
27%
took first-generation
antipsychotics
ADVERSE REACTIONS BY DOSE IN KINECT 3
Treatment-emergent adverse reactions with incidence ≥2% in all patients treated with INGREZZA and at a higher incidence than placebo during the 6-week treatment period in a pivotal study (safety population)2
| Adverse Reaction |
All INGREZZA treated (n=151) (%) |
INGREZZA 40 mg (n=72) (%) |
INGREZZA 80 mg (n=79) (%) |
Placebo (n=76) (%) |
|---|---|---|---|---|
| Overall | 45.7% | 40.3% | 50.6% | 43.4% |
| Somnolence | 5.3% | 5.6% | 5.1% | 3.9% |
| Akathisia | 3.3% | 4.2% | 2.5% | 1.3% |
| Dry mouth | 3.3% | 6.9% | 0.0% | 1.3% |
| Arthralgia | 2.6% | 1.4% | 3.8% | 1.3% |
| Dyskinesia | 2.0% | 0.0% | 3.8% | 0.0% |
| Vomiting | 2.0% | 0.0% | 3.8% | 0.0% |
| Anxiety | 2.0% | 1.4% | 2.5% | 0.0% |
| Fatigue | 2.0% | 2.8% | 1.3% | 1.3% |
| Weight increase | 2.0% | 1.4% | 2.5% | 0.0% |
| Insomnia | 2.0% | 1.4% | 2.5% | 1.3% |
The most common types of concomitant medications were2,3:
- Antipsychotics (85.5%)
- Antidepressants (66.5%)
- Anticholinergics (37.0%)
- Antiepileptics (35.2%)
- Anxiolytics (27.7%)
- ACE inhibitors (25.1%)
PSYCHIATRIC STATUS GENERALLY REMAINED STABLE DURING THE KINECT 3 STUDY2
Safety assessments of psychiatric disorders from baseline through 6 weeks3
| Disorder | Observed increase or worsening | Measure |
|---|---|---|
| Schizophrenia | No | PANSSa |
| Mania | No | YMRSb |
| Suicidal ideation/ behavior |
No | C-SSRSc |
| Depression | No | CDSS,d MADRSe |
| a | Mean change in Positive and Negative Syndrome Scale (PANSS) total score from baseline at 6 weeks was −0.4 for INGREZZA 40 mg, −0.8 for INGREZZA 80 mg, and ±0.0 for placebo. |
| b | Mean change in Young Mania Rating Scale (YMRS) total score from baseline at 6 weeks was −0.4 for INGREZZA 40 mg, −1.4 for INGREZZA 80 mg, and +0.5 for placebo. |
| c | Incidence of suicidal ideation or behavior on the Columbia Suicide Severity Rating Scale (C-SSRS) was 5.6% for INGREZZA 40 mg, 2.5% for INGREZZA 80 mg, and 5.3% for placebo. |
| d | Mean change in Calgary Depression Scale for Schizophrenia (CDSS) total score from baseline at 6 weeks was −0.5 for INGREZZA 40 mg, −0.4 for INGREZZA 80 mg, and −0.1 for placebo. |
| e | Mean change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline at 6 weeks was ±0.0 for INGREZZA 40 mg, −1.5 for INGREZZA 80 mg, and +1.2 for placebo. |
Drug-induced parkinsonism across the study period, as measured by the Simpson-Angus Scale3
In the 3 placebo-controlled clinical studies in patients with TD, the incidence of parkinson-like adverse events was 3% of patients treated with INGREZZA and <1% of patients treated with placebo. The mean change in Simpson-Angus Scale score from baseline at 6 weeks across studies was1,3,f:
- 0.0 for INGREZZA 40 mg
- −0.1 for INGREZZA 80 mg
- −0.1 for placebo
| f | 40 mg data include doses of 40 mg and 50 mg; 80 mg data include doses of 75 mg and 80 mg. |
SEE LONG-TERM SAFETY AND TOLERABILITY WITH INGREZZA
Review results of the KINECT 4 study—a phase 3, long-term, open-label study evaluating the safety and tolerability of once-daily INGREZZA.4
REFERENCES:
- INGREZZA [package insert]. San Diego, CA: Neurocrine Biosciences, Inc.
- Hauser RA, Factor SA, Marder SR, et al. KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174(5):476-484.
- Data on file. Neurocrine Biosciences, Inc.
- Marder SR, Singer C, Lindenmayer JP, et al. A phase 3, 1-year, open-label trial of valbenazine in adults with tardive dyskinesia. J Clin Psychopharmacol. 2019;39(6):620-627.