A Clinical Study to Evaluate CAD-1883 in Essential Tremor

NCT03688685 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CAD1883-201
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 7

Brief Summary

This is an open-label study designed to evaluate the safety, tolerability and efficacy of CAD-1883, a positive allosteric modulator of the SK channel, administered twice daily orally to adult patients with ET. Patients with the diagnosis of ET based on the Movement Disorder Society (MDS) criteria with a documented severity of tremor based on the clinician-administered TETRAS Performance Subscale are eligible to be enrolled in the study.

Conditions

Essential Tremor

Keywords

ET; Essential Tremor

Outcome Measures

Primary Outcomes (1)

• Evaluate the Occurrence and Severity of Treatment Emergent AEs.

  Number of subjects who experienced TEAEs and the severity of those TEAEs.

  Time of signed informed consent until 21 days after first treatment

Study Arms (1)

Open-label study of CAD-1883

EXPERIMENTAL

Open-label study designed to evaluate the safety, tolerability, and efficacy of CAD-1883 administered twice daily orally to adult subjects with ET

Drug: CAD-1883

Interventions

CAD-1883 DRUG

Treatment groups receiving twice-daily oral dosing of CAD-1883 for a treatment period of 14 days.

Open-label study of CAD-1883

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult subjects aged between 18 and 75 years old, inclusive, with history of tremor that fulfills the diagnostic criteria of ET according to Movement Disorder Society (MDS) Consensus Statement on the classification of tremors from the task force on tremor of the International Parkinson and Movement Disorder Society (Bhatia, 2018).
• Duration of ET illness since the first symptoms were noticeable of at least 3 years or more prior to screening, based on the subject's self-report, with onset prior to age 65 years old, per the Principal Investigator's assessment during screening.
• Except for ET, subjects must be otherwise healthy as determined by the Investigator, based upon a medical evaluation including medical history, physical examination, laboratory tests, and 12-lead ECG.
• Subjects are able to understand study activities required, can give written informed consent, and are willing to comply with the requirements and restrictions of the study.
• Women of childbearing potential must undertake a pregnancy test with documented negative serum pregnancy test at Screening and negative urine pregnancy test result at Pre-dose, Days 7 and 14 before administration of the study drug, and then at the Follow-up visit (Day 21).
• Postmenopausal women must have had ≥365 days of spontaneous amenorrhea, with documented follicle-stimulating hormone (FSH) ≥38 IU/mL, prior to screening. If needed, per Investigator's judgment, FSH level can be performed at Screening.
• Surgically sterile women must have documentation of a hysterectomy, bilateral ovariectomy, or bilateral tubal ligation.
• Female subjects with reproductive potential and male subjects with reproductive potential or who have female partners of reproductive potential, must agree to use two effective methods of contraception from signing informed consent until 90 days after the last dose of study drug. Acceptable forms of contraception include double barrier (ie, condom with spermicide); surgically sterilized partner (180-day minimum); or abstinence.

You may not qualify if:

• Prior or ongoing medical condition or any abnormal finding on the Screening visit physical exam, ECG, laboratory testing that, in the Investigator's opinion, could adversely affect the safety of the subject or the conduct of the study assessments.
• Any neurological abnormality other than ET upon neurological exam, including dystonia, ataxia, or any other neurodegenerative disease, including multiple sclerosis or Parkinson's disease.
• Significant cognitive impairment or dementia that, in the opinion of the Investigator, would interfere with participation in the study.
• An unstable thyroid condition that, per the Investigator's judgment, has not stabilized over the past 90 days prior to screening. This includes current clinical history of hypo- or hyperthyroidism, thyrotoxicosis or significant abnormality of thyroid function testing at Screening.
• History of, or evidence of psychogenic tremor at Screening.
• History of anaphylaxis, hypersensitivity reactions (including to any of CAD-1883 excipients), or clinically significant drug allergies.
• Alkaline phosphatase, aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT) level \>2.0 x upper limit of normal (ULN) at Screening and/or at Pre-dose.
• Serum creatinine \>120 μmol/L and/or creatinine clearance \<60 mL/min (according to Cockcroft-Gault formula) at Screening and/or at Pre-dose.
• Total bilirubin \>2.0 x ULN at Screening and/or at Pre-dose. Note: isolated bilirubin \>2.0 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35%.
• History of Long QT syndrome and/or QTcF (Fridericia's correction) interval \>450 msec (males) or \>470 msec (females) per 12-lead ECG done at Screening.
• History of Alcohol Use Disorder per Diagnostic Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria.
• History of human immunodeficiency virus (HIV) infection or positive screening result for: HIV 1 or 2 antibodies, hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), or hepatitis C virus antibody (HCVAb).
• Has a diagnosis of epilepsy or any history of seizure as an adult, head trauma, stroke, transient ischemic attack within 1 year prior to Screening, unexplained loss of consciousness within 1 year prior to Screening, or any lifetime history of asymptomatic or symptomatic orthostatic hypotension (eg, postural syncope).
• History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class 3 or 4), or clinically significant conduction abnormalities (eg, unstable atrial fibrillation) within 1 year prior to screening.
• Any major psychiatric disorder that is uncontrolled (for the past 90 days) that, per the Investigator's judgment, can interfere with any of the study procedures.

Sponsors & Collaborators

• Cadent Therapeutics: lead

Study Sites (7)

Cadent Investigational Site

Anniston, Alabama, 36207, United States

Location

Cadent Investigational Site

Rogers, Arkansas, 72758, United States

Location

Cadent Investigational Site

San Diego, California, 92103, United States

Location

Cadent Investigational Site

Hallandale, Florida, 33009, United States

Location

Cadent Investigational Site

Farmington Hills, Michigan, 48334, United States

Location

Cadent Investigational Site

St Louis, Missouri, 63141, United States

Location

Cadent Investigational Site

Dayton, Ohio, 45400, United States

Location

MeSH Terms

Conditions

Essential Tremor

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Cadent Therapeutics (A Novartis Company)
• Organization: Cadent Therapeutics (A Novartis Company)

Novartis.email@novartis.com

1-888-669-6682

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2018
• First Posted: September 28, 2018
• Study Start: January 23, 2019
• Primary Completion: September 10, 2019
• Study Completion: September 24, 2019
• Last Updated: August 5, 2021
• Results First Posted: July 9, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)