Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities

NCT06107829 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: STUDY20221555
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this open-label clinical trial is to test the safety and efficacy of valbenazine treatment in patients with Intellectual/Developmental Disability (IDD) who have a diagnosis of Tardive dyskinesia (TD). The main questions this study aims to answer are:

• Does valbenazine treatment of TD in the previously untreated patient population of adults with IDD produce comparable amelioration of signs of movement disorder as what has historically been reported in adults without IDD?
• Is valbenazine treatment of TD in persons with IDD as safe as what has historically been reported in adults without IDD?
• Does valbenazine treatment improve Quality of Life (QOL) in persons with IDD and TD treated with valbenazine?
• Does valbenazine treatment produce positive change in Activities of Daily Living (ADLs) in persons with IDD and TD?
• Does valbenazine treatment of TD in persons with IDD reduce caregiver burden? In this study, 25 participants with IDD and TD will undergo valbenazine treatment for 24 weeks. The participants will be seen for a total of 5 visits: at baseline, and at follow up visits at 3 weeks, 6 weeks, 12 weeks, and 24 weeks. This study does not include a comparison group. Therefore, researchers will compare the response of the study participants to valbenazine treatment with those from a previous reported work that resulted in the FDA approval of this medication.

Conditions

Tardive Dyskinesia; Intellectual Disability; Developmental Disabilities

Keywords

valbenazine; movement disorders; antipsychotic medication adverse effects; Abnormal Involuntary Movement Scale; quality of life; adaptive behavior; caregiver burden; selective vesicular monoamine transporter 2 inhibitor

Outcome Measures

Primary Outcomes (1)

• Change in AIMS total scores of items 1-7

  The Abnormal Involuntary Movement Scale (AIMS) has been used for many years as the gold standard for this purpose and the amount of improvement (change in movement intensity, and reduction in AIMS scores) have been assessed clinical significance in rating improvement. A number of authors have noted the difficulty in using the AIMS in persons with IDD who cannot cooperate fully in the examination process. For this reason, some have suggested using videotaped AIMS exams as a methodology for more accurately quantifying change. Videotaping of exams pre- and post-treatment for blind rating of improvement has been a methodology utilized in a number of recent studies of valbenazine. The minimum value of the AIMS total score of items 1-7 is 0 and the maximum value is 49. Higher total AIMS scores mean worse outcomes.

  Baseline and 24 weeks from start of treatment

Secondary Outcomes (6)

• Change in AIMS item 8 scores

  Baseline and 24 weeks from start of treatment

• CGI-C

  Baseline and 24 weeks from start of treatment

• CaGI-C

  Baseline and 24 weeks from start of treatment

• Change in ABC-I score

  Baseline and 24 weeks from start of treatment

• Change in W-ADL score

  Baseline and 24 weeks from start of treatment

Other Outcomes (3)

• Change Simpson-Angus Scale for EPS

  Baseline and 24 weeks from start of treatment

• Change in Barnes Akathisia Scale

  Baseline and 24 weeks from start of treatment

• Assessment of electrocardiogram (EKG)-derived QT/QTc intervals

  Baseline and 24 weeks from start of treatment

Study Arms (1)

Valbenazine

EXPERIMENTAL

This an open-label study in which all participants will have their valbenazine dose titrated from 40 mg to 80 mg per day, which will remain the valbenazine dose through end of study, unless interrupted by adverse events. Participants taking valbenazine who are concurrently taking strong CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion, duloxetine) will continue their valbenazine dose at 40 mg per day through end of study. Participants taking valbenazine who are concurrently taking strong CYP3A4 inhibitors (ketoconazole, fluconazole, cimetidine, verapamil) will continue their valbenazine dose at 40 mg per day through end of study.

Drug: Valbenazine Oral Capsule

Interventions

Valbenazine Oral Capsule DRUG

Open-label twenty-four-week treatment with valbenazine oral capsules (up to 80 mg/day) to test the safety and effectiveness of this medication in ameliorating the signs of tardive dyskinesia in persons with intellectual disability.

Also known as: Ingrezza

Valbenazine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of IDD (IQ \< 70; social/adaptive dysfunction, onset \< age 22) as per DSM-5
• Eligible to receive valbenazine according to current product labeling.
• Willing to remain on stable doses of all psychotropics for 24 weeks of study. If female of childbearing age, practicing acceptable form for birth control throughout study duration.
• Subject able to comply with scheduled visits and assessments.
• Consent of subject, or legally authorized representative to study protocol.

You may not qualify if:

• Previous treatment with a VMAT2 inhibitor (tetrabenazine, valbenazine, or deutetrabenazine).
• Treatment with any investigational drug in the 30 days prior to study entry.
• Currently taking a strong CYP3A4 inducer such as carbamazepine, phenobarbital, diphenylhydantoin, or primidone.
• Any unstable medical condition in the 60 days prior to study entry.
• Pregnant or breast-feeding.
• Inability to take study medication.
• History of neuroleptic malignant syndrome.
• History of long QTc on electrocardiogram, bundle branch block (BBB), atrioventricular block, serious cardiac arrhythmia, or heart failure.
• QTc on EKG \> 450 msec (Fredericia formula) on EKG within 3 months prior to study entry.
• History of substance abuse or dependence in the 3 months prior to study entry.
• Significant risk of suicide or dangerous aggression to others at time of or 3 months prior to study entry.

Sponsors & Collaborators

• Stephen Ruedrich: lead
• Neurocrine Biosciences: collaborator

Study Sites (1)

University Hospitals of Cleveland

Cleveland, Ohio, 44106, United States

Location

Related Publications (29)

• Aman MG (2012) Aberrant Behavior Checklist: Current Identity and Future Developments. Clin Exp Pharmacol 2:e114. doi:10.4172/2161- 1459.1000e114

  BACKGROUND

• Barnes TR. The Barnes Akathisia Rating Scale--revisited. J Psychopharmacol. 2003 Dec;17(4):365-70. doi: 10.1177/0269881103174013.

  PMID: 14870947 BACKGROUND

• Bowring DL, Totsika V, Hastings RP, Toogood S, McMahon M. Prevalence of psychotropic medication use and association with challenging behaviour in adults with an intellectual disability. A total population study. J Intellect Disabil Res. 2017 Jun;61(6):604-617. doi: 10.1111/jir.12359. Epub 2017 Jan 16.

  PMID: 28090687 BACKGROUND

• Correll CU, Kane JM, Citrome LL. Epidemiology, Prevention, and Assessment of Tardive Dyskinesia and Advances in Treatment. J Clin Psychiatry. 2017 Sep/Oct;78(8):1136-1147. doi: 10.4088/JCP.tv17016ah4c.

  PMID: 29022654 BACKGROUND

• de Kuijper GM, Hoekstra PJ. Physicians' reasons not to discontinue long-term used off-label antipsychotic drugs in people with intellectual disability. J Intellect Disabil Res. 2017 Oct;61(10):899-908. doi: 10.1111/jir.12385. Epub 2017 May 30.

  PMID: 28560761 BACKGROUND

• de Kuijper GM, Hoekstra PJ. Assessment of Drug-Associated Extrapyramidal Symptoms in People With Intellectual Disability: A Comparison of an Informant-Based Scale With Clinical Rating Scales. J Clin Psychopharmacol. 2016 Oct;36(5):508-12. doi: 10.1097/JCP.0000000000000558.

  PMID: 27529770 BACKGROUND

• Fodstad JC, Bamburg JW, Matson JL, Mahan S, Hess JA, Neal D, Holloway J. Tardive dyskinesia and intellectual disability: an examination of demographics and topography in adults with dual diagnosis and atypical antipsychotic use. Res Dev Disabil. 2010 May-Jun;31(3):750-9. doi: 10.1016/j.ridd.2010.01.017. Epub 2010 Mar 5.

  PMID: 20207106 BACKGROUND

• Guy W (1976). ECDEU Assessment Manual for Psychopharmacology: Revised (DHEW publication number ADM 76-338). Rockville, MD, Us Department of Health, Education and Welfare, PHS, ADAMHA, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs, 1976:534-537.

  BACKGROUND

• Hauser RA, Factor SA, Marder SR, Knesevich MA, Ramirez PM, Jimenez R, Burke J, Liang GS, O'Brien CF. KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. Am J Psychiatry. 2017 May 1;174(5):476-484. doi: 10.1176/appi.ajp.2017.16091037. Epub 2017 Mar 21.

  PMID: 28320223 BACKGROUND

• Hérbert, R., Bravo, G., & Préville, M. (2000). Reliability, validity, and reference values of the Zarit Burden Interview for assessing informal caregivers of community-dwelling older persons with dementia. Canadian Journal on Aging, 19, 494-507.

  BACKGROUND

• Kane JM, Correll CU, Nierenberg AA, Caroff SN, Sajatovic M; Tardive Dyskinesia Assessment Working Group. Revisiting the Abnormal Involuntary Movement Scale: Proceedings From the Tardive Dyskinesia Assessment Workshop. J Clin Psychiatry. 2018 May/Jun;79(3):17cs11959. doi: 10.4088/JCP.17cs11959.

  PMID: 29742330 BACKGROUND

• Maenner MJ, Smith LE, Hong J, Makuch R, Greenberg JS, Mailick MR. Evaluation of an activities of daily living scale for adolescents and adults with developmental disabilities. Disabil Health J. 2013 Jan;6(1):8-17. doi: 10.1016/j.dhjo.2012.08.005. Epub 2012 Oct 17.

  PMID: 23260606 BACKGROUND

• Matson JL, Fodstad JC, Neal D, Dempsey T, Rivet TT. Risk factors for tardive dyskinesia in adults with intellectual disability, comorbid psychopathology, and long-term psychotropic use. Res Dev Disabil. 2010 Jan-Feb;31(1):108-16. doi: 10.1016/j.ridd.2009.08.002. Epub 2009 Aug 31.

  PMID: 19720497 BACKGROUND

• McEvoy J, Gandhi SK, Rizio AA, Maher S, Kosinski M, Bjorner JB, Carroll B. Effect of tardive dyskinesia on quality of life in patients with bipolar disorder, major depressive disorder, and schizophrenia. Qual Life Res. 2019 Dec;28(12):3303-3312. doi: 10.1007/s11136-019-02269-8. Epub 2019 Aug 21.

  PMID: 31435866 BACKGROUND

• Morton RO, Morton LC, Fedora R. Recognition and Treatment of Tardive Dyskinesia in Individuals with Intellectual Disability. Case Rep Psychiatry. 2020 Dec 11;2020:8886980. doi: 10.1155/2020/8886980. eCollection 2020.

  PMID: 33414976 BACKGROUND

• Ruedrich SL. (2016). Psychopharmacology. In Hemmings C & Bouras N (eds.) Psychiatric and Behavioural Disorders in Intellectual and Developmental Disabilities, Third Edition, Cambridge University Press, Cambridge, UK, 139-150.

  BACKGROUND

• Ruedrich SL (2010). Mental Illness in O'Hara J, McCarthy J, and Bouras N. (eds.) Intellectual Disability and Ill Health: A Review of the Evidence, Cambridge University Press, Cambridge UK, 165-177.

  BACKGROUND

• Ruedrich SL, Diana L, Rossvanes CF, Toliver J. (2005). The abnormal involuntary movement scale (AIMS) and tardive dyskinesia in persons with developmental disability: the benefit of videotaped exams. Mental Health Aspects of Developmental Disabilities 8(3)94-99.

  BACKGROUND

• Schmidt S, Power M, Green A, Lucas-Carrasco R, Eser E, Dragomirecka E, Fleck M. Self and proxy rating of quality of life in adults with intellectual disabilities: results from the DISQOL study. Res Dev Disabil. 2010 Sep-Oct;31(5):1015-26. doi: 10.1016/j.ridd.2010.04.013. Epub 2010 May 15.

  PMID: 20478692 BACKGROUND

• Schooler NR, Kane JM. Research diagnoses for tardive dyskinesia. Arch Gen Psychiatry. 1982 Apr;39(4):486-7. doi: 10.1001/archpsyc.1982.04290040080014. No abstract available.

  PMID: 6121550 BACKGROUND

• Sheehan R, Horsfall L, Strydom A, Osborn D, Walters K, Hassiotis A. Movement side effects of antipsychotic drugs in adults with and without intellectual disability: UK population-based cohort study. BMJ Open. 2017 Aug 3;7(8):e017406. doi: 10.1136/bmjopen-2017-017406.

  PMID: 28775195 BACKGROUND

• Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl. 1970;212:11-9. doi: 10.1111/j.1600-0447.1970.tb02066.x. No abstract available.

  PMID: 4917967 BACKGROUND

• Solmi M, Pigato G, Kane JM, Correll CU. Clinical risk factors for the development of tardive dyskinesia. J Neurol Sci. 2018 Jun 15;389:21-27. doi: 10.1016/j.jns.2018.02.012. Epub 2018 Feb 5.

  PMID: 29439776 BACKGROUND

• Stacy M, Sajatovic M, Kane JM, Cutler AJ, Liang GS, O'Brien CF, Correll CU. Abnormal involuntary movement scale in tardive dyskinesia: Minimal clinically important difference. Mov Disord. 2019 Aug;34(8):1203-1209. doi: 10.1002/mds.27769. Epub 2019 Jun 24.

  PMID: 31234240 BACKGROUND

• Tsiouris JA. Pharmacotherapy for aggressive behaviours in persons with intellectual disabilities: treatment or mistreatment? J Intellect Disabil Res. 2010 Jan 1;54(1):1-16. doi: 10.1111/j.1365-2788.2009.01232.x. Epub 2009 Dec 8.

  PMID: 20122096 BACKGROUND

• Townsend-White C, Pham AN, Vassos MV. Review: a systematic review of quality of life measures for people with intellectual disabilities and challenging behaviours. J Intellect Disabil Res. 2012 Mar;56(3):270-84. doi: 10.1111/j.1365-2788.2011.01427.x. Epub 2011 Jun 17.

  PMID: 21679329 BACKGROUND

• Whiteney C and Evered JA (2022). The Qualitative Research Distress Protocol: A Participant-Centered Tool for Navigating Distress During Data Collection. International Journal of Qualitative Methods Volume 21:1-9.

  BACKGROUND

• Woods SW, Morgenstern H, Saksa JR, Walsh BC, Sullivan MC, Money R, Hawkins KA, Gueorguieva RV, Glazer WM. Incidence of tardive dyskinesia with atypical versus conventional antipsychotic medications: a prospective cohort study. J Clin Psychiatry. 2010 Apr;71(4):463-74. doi: 10.4088/JCP.07m03890yel. Epub 2010 Feb 9.

  PMID: 20156410 BACKGROUND

• Yu J, Yap P, Liew TM. The optimal short version of the Zarit Burden Interview for dementia caregivers: diagnostic utility and externally validated cutoffs. Aging Ment Health. 2019 Jun;23(6):706-710. doi: 10.1080/13607863.2018.1450841. Epub 2018 Mar 19.

  PMID: 29553806 BACKGROUND

MeSH Terms

Conditions

Tardive Dyskinesia; Intellectual Disability; Developmental Disabilities; Movement Disorders; Caregiver Burden

Interventions

valbenazine

Condition Hierarchy (Ancestors)

Dyskinesia, Drug-Induced; Dyskinesias; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Mental Disorders; Stress, Psychological; Behavioral Symptoms; Behavior

Study Officials

• Stephen Ruedrich, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: October 25, 2023
• First Posted: October 30, 2023
• Study Start: January 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: October 24, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: From 12 months after publication until three years afterwards.
• Access Criteria: Any request must be approved by the corresponding author and the principal investigator. Each request will be checked for compatibility with regulatory (institutional review board) requirements as well as compatibility with participant informed consent.

Locations

US (1)