Clinical trial NCT00292227: Cardiac Effects of Rotigotine Transdermal System in Subjects With Advanced-stage Idiopathic Parkinson's Disease
Official title: Double-blind, Randomized, Placebo- and Positive-controlled, Parallel-group Trial to Assess the Potential Electrocardiographic Effects of Rotigotine Transdermal System up to 120 cm2/54.0 mg/Day in Subjects With Advanced-stage Idiopathic Parkinson's Disease: A Thorough QT/QTc Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Keywords: advanced-stage idiopathic Parkinson's disease
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2006-02-15
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to assess whether rotigotine has an effect on the electrical activity of the heart. Moxifloxacin infusion is used as positive control to assess assay sensitivity.


Eligibility criteria: Inclusion Criteria:

* Male or female at least 18 years of age
* Advanced-stage idiopathic Parkinson's disease requiring treatment with levodopa.
* Nonchildbearing potential

Exclusion Criteria:

* Atypical Parkinson's syndrome(s).
* History of pallidotomy, thalamotomy, deep brain stimulation, or fetal tissue transplant.
* Significant tremor or dyskinesias.
* Severe dysfunction of the autonomic nervous system.
* History of transient ischemic attack or stroke within the last 12 months.
* Conduction abnormality or relevant cardiac dysfunction and/or myocardial infarction within last 12 months.
* History or current condition of additional risk factors for Torsade de Pointes (eg, heart failure, hypokalemia), or a family history of long QT syndrome and/or of Torsade de Pointes.
* No stable sinus rhythm: more than 20 ectopics/h.
* Any other clinically relevant ECG abnormality.
* History or current condition of epilepsy and/or seizures.
* History or current condition of atopic or eczematous dermatitis, psoriasis, or another active skin disease.
* History or current condition of symptomatic orthostatic hypotension.
* History or current condition of significant skin hypersensitivity to adhesives or other transdermal products or recent unresolved contact dermatitis.
* History of glucose 6-phosphate dehydrogenase deficiency.
* History of tendonitis or tendon rupture with quinolone antibiotics.
* Renal or hepatic dysfunction.
* Treatment with dopamine agonists, MAO A inhibitors, reserpine, or alpha-methyldopa
* Therapy known to produce a nontrivial prolongation of the QT interval.

Primary outcomes:
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI at Time of Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 20:00h, Day 42 20:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 1 Hour After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 21:00h, Day 42 21:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 2 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 22:00h, Day 42 22:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 3 Hours After Patch Application on Day 42(Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 23:00h, Day 42 23:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 4 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 00:00h, Day 43 00:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 5 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 1:00h, Day 43 1:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 6 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 2:00h, Day 43 2:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 7 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 3:00h, Day 43 3:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 8 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 4:00h, Day 43 4:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 9 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 5:00h, Day 43 5:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 10 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 6:00h, Day 43 6:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 11 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 7:00h, Day 43 7:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 12 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 8:00h, Day 43 8:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 13 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 9:00h, Day 43 9:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 14 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 10:00h, Day 43 10:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 15 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 11:00h, Day 43 11:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 16 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 12:00h, Day 43 12:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 17 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 13:00h, Day 43 13:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 18 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 14:00h, Day 43 14:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 19 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 15:00h, Day 43 15:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 20 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 16:00h, Day 43 16:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 21 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 17:00h, Day 43 17:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 22 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 18:00h, Day 43 18:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 23 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 19:00h, Day 43 19:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTc Based on the QTcI 24 Hours After Patch Application on Day 42 (Rotigotine Dose of 54 mg/Day) (Parallel-group Comparison)
timeFrame: Baseline (Day -2/ Day -1) 20:00h, Day 43 20:00h
Secondary outcomes:
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 2 Hours Before Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 8:00h, Day 32/ Day 39 8:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 1 Hour Before Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 9:00h, Day 32/ Day 39 9:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI at Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 10:00h, Day 32/ Day 39 10:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 1 Hour After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 11:00h, Day 32/ Day 39 11:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 2 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 12:00h, Day 32/ Day 39 12:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 3 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 13:00h, Day 32/ Day 39 13:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 4 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 14:00h, Day 32/ Day 39 14:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 5 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 15:00h, Day 32/ Day 39 15:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 6 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 16:00h, Day 32/ Day 39 16:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 7 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 17:00h, Day 32/ Day 39 17:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 8 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 18:00h, Day 32/ Day 39 18:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 9 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 19:00h, Day 32/ Day 39 19:00h
measure: Time-matched Change From Baseline (Average of Day -2 and Day -1) in QTcI 10 Hours After Start of Infusion on Day 32 or Day 39 (Positive Control) and Respective Day 39 or Day 32 (Corresponding Placebo) (Cross-over Comparison)
timeFrame: Baseline (Day -2/ Day -1) 20:00h, Day 32/ Day 39 20:00h
Other outcomes:
Locations:
city: Bloemfontein
country: South Africa
facility: Farmovs-Parexel (Pty) Ltd
city: George
country: South Africa
facility: Qdot, a division of Parexel International DA (Pty) Ltd.
Study officials:
affiliation: +1 877 822 9493 (UCB)
name: UCB Clinical Trial Call Center
role: STUDY_DIRECTOR
References:
citation: Malik M, Andreas JO, Hnatkova K, Hoeckendorff J, Cawello W, Middle M, Horstmann R, Braun M. Thorough QT/QTc study in patients with advanced Parkinson's disease: cardiac safety of rotigotine. Clin Pharmacol Ther. 2008 Nov;84(5):595-603. doi: 10.1038/clpt.2008.143. Epub 2008 Jul 23.
citation: Elshoff JP, Braun M, Andreas JO, Middle M, Cawello W. Steady-state plasma concentration profile of transdermal rotigotine: an integrated analysis of three, open-label, randomized, phase I multiple dose studies. Clin Ther. 2012 Apr;34(4):966-78. doi: 10.1016/j.clinthera.2012.02.008. Epub 2012 Mar 7.