Phase 2
Completed N=27
Study to Assess the Safety, Tolerability and Preliminary Efficacy of NLX-112 Versus Placebo in L-dopa-induced Dyskinesia
Medication-Induced Dyskinesia
Source: ClinicalTrials.gov NCT05148884 ↗
Enrolled (actual)
27
Serious AEs
3.7%
Results posted
Apr 2024
Primary outcomePrimary: Number of Participants With Adverse Events (AEs) — 16; 7; 0; 1 Participants
Summary
This is a double-blind, randomized, placebo-controlled Phase 2a study evaluating the safety, tolerability, and preliminary efficacy of up to 2 mg/day (1 mg BID) of NLX-112 versus placebo in patients with moderate to severe L-DOPA induced dyskinesia (LID) in Parkinson's disease (PD). NLX-112 will be up-titrated to either 2 mg/day or to the highest well-tolerated dose less than 2 mg/day over 4 weeks, maintained at the well-tolerated dose for an additional 2 weeks, and then down-titrated over 2 weeks.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs) |
16; 7; 0; 1; 0; 0 | — |
| PRIMARY Number of Participants With Any Clinically Significant Changes From Baseline in Electrocardiogram (ECG) |
0; 0 | — |
| PRIMARY Number of Patients With Any Clinically Significant Changes From Baseline in Vital Signs |
2; 0 | — |
| PRIMARY Number of Patients With Any Clinically Significant Changes From Baseline in Safety Laboratory Parameters |
2; 1 | — |
| PRIMARY Number of Patients With Clinically Significant Abnormalities in Physical Examinations |
8; 1; 7; 4 | — |
| PRIMARY Number of Patients With Suicidal Ideation/Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) |
0; 0 | — |
| SECONDARY Change From Baseline at the Final Efficacy Clinic Visit (Day 42), After a 150% L-dopa Dose Challenge, in the Unified Dyskinesia Rating Scale (UDysRS) Total Score - Change From Baseline |
31.6; 39.9; 25.3; 37.4 | 0.0016 sig |
| SECONDARY Change From Baseline in UDysRS Total Score at Day 28, After a 150% L-DOPA Dose Challenge - Change From Baseline |
31.6; 39.9; 27.5; 37.9 | 0.0281 sig |
| SECONDARY Change From Baseline in Total Objective Score (Parts 3, 4) of the UDysRS at Day 28 and Day 42, After a 150% L-DOPA Dose Challenge - Change From Baseline |
15.5; 18.1; 13.8; 17.1; 12.4; 18.0 | — |
| SECONDARY Change From Baseline in ON Time Without Troublesome Dyskinesia (ON Without Dyskinesia Plus ON With Non-troublesome Dyskinesia) Based on a PD Home Dyskinesia Diary - Change From Baseline |
0.576; 0.548; 0.633; 0.591; 0.648; 0.564 | — |
| SECONDARY Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Scores (Part III, Motor Examination) - Change From Baseline |
17.5; 17.0; 13.9; 18.3; 13.9; 17.1 | — |
| SECONDARY Change From Baseline in UPDRS Combined Scores (Parts I, II, III and IV) - Change From Baseline |
37.0; 41.3; 30.5; 37.7; 31.3; 37.4 | — |
| SECONDARY Number of Patients in Each Category of Clinical Global Impression of Change (CGI-C) in Overall PD Symptoms |
3; 2; 8; 2; 3; 2 | — |
| SECONDARY Change From Baseline in Dyskinesia Scores Measured by the Kinesia 360 (Great Lakes Neurotechnologies, Inc) Wearable Dyskinesia Assessment System - Absolute Change From Baseline |
0.1807; 0.2855; -0.06517; -0.009172; -0.009327; -0.01630 | — |
Eligibility Criteria
Inclusion Criteria
- Patient is 30 - 85 years old (inclusive) with a diagnosis of idiopathic PD according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnosis criteria.
- PD patient is stably and optimally treated with L-DOPA; other anti-PD treatments are allowed if used for at least 4 weeks of previous continuous treatment.
- Patient agrees to be challenged with 150% of their normal L-DOPA dose (maximum L-DOPA dose 250 mg) 30 minutes prior to efficacy assessments at baseline (Visit 2) and at the 2 efficacy clinic visits (Visits 6 and 7).
- PD patient exhibits troublesome peak-dose LID, confirmed by a score of at least 1 on part IV, item 33 (disability) of the UPDRS at screening (Visit 1) and at Day 1 (baseline, Visit 2).
- At least 90 minutes in total for each 24-hour period during 2 days are indicated as "ON with troublesome dyskinesia" (according to the PD Home Dyskinesia Diary) prior to Day 1 (baseline, Visit 2).
- Patient (and/or caregiver) demonstrates ability to accurately complete the PD Home Dyskinesia Diary entries during the screening visit.
- Patient can read well enough to understand the informed consent document and other subject materials.
- Female patients of child-bearing potential must have a negative urine pregnancy test at screening (Visit 1) and on Day 1 (Visit 2), must agree to avoid pregnancy during the study, and must practice abstinence (only allowed when this is the preferred and usual lifestyle of the subject) or must agree to use a highly effective method of contraception with a failure rate of < 1% to prevent pregnancy (combined [oestrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device [IUD] or intrauterine hormone-releasing system [IUS]) starting from 4 weeks prior to administration of the study drug and continuing during the course of the study until 4 weeks after last after IMP administration. Female subjects must agree to refrain from donating eggs from the date of dosing until 3 months after dosing with the IMP. Their male partner must agree to use a condom during the same time frame if he has not undergone vasectomy.
Females of non-childbearing potential are defined as pre-menopausal females who are sterilised (tubal ligation or permanent bilateral occlusion of fallopian tubes); or females who have undergone hysterectomy or bilateral oophorectomy; or post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with detection of follicle stimulating hormone [FSH] 25-140 IE/L is confirmatory).
Male patients must be either vasectomised, consent to use condom or practice sexual abstinence to prevent pregnancy and drug exposure of a partner and refrain from donating sperm from the date of dosing until 3 months after dosing with the IMP. Their female partner of child-bearing potential must use highly effective contraceptive methods with a failure rate of < 1% to prevent pregnancy (see above) during the same period.
Exclusion Criteria
- Patient has severe PD with a Hoehn and Yahr stage = 5.
- Patient has unstable medical status, prior brain surgery against tumors or hemorrhage (excluding deep brain stimulation [DBS], i.e., DBS patients will be allowed to be enrolled) or is scheduled to receive surgery during the trial period.
- Patient has orthostatic hypotension: a decrease in systolic blood pressure (at least 20 mm Hg) or diastolic blood pressure (at least 10 mm Hg) within 3 minutes of the patient standing up, compared to pressures obtained while in a sitting position for at least 5 minutes. At screening and baseline visits (Visit 1 and Visit 2), vital signs to assess orthostatic hypotension will be conducted in triplicate, 15-20 minutes apart, with the average of the 3 assessments used for exclusion.
- Patient has dementia (MMS
Data sourced from ClinicalTrials.gov (NCT05148884). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.