Trial Outcomes & Findings for Dose Escalating Study of Rotigotine in Pediatric Subjects With Restless Legs Syndrome (NCT NCT01495793)

NCT ID: NCT01495793

Last Updated: 2018-04-04

Results Overview

CL/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma. For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 42 participants
• Primary outcome timeframe: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28
• Results posted on: 2018-04-04

Participant Flow

This was a multicenter study in which 42 subjects were enrolled and 24 treated at 8 sites in the USA.

In total 42 subjects signed the informed consent and were enrolled into the study (Enrolled Set). 24 of these subjects were treated with medication. The sample size of 24 subjects was sufficient to target a 95% confidence interval and the calculation was based on a previous study. Participant Flow refers to the 24 treated subjects (Safety Set).

Participant milestones

Measure	Rotigotine In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
Overall Study STARTED	24
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Rotigotine In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
Overall Study Lost to Follow-up	1
Overall Study Violation of inclusion criteria	1

Baseline Characteristics

Dose Escalating Study of Rotigotine in Pediatric Subjects With Restless Legs Syndrome

Baseline characteristics by cohort

Measure	Rotigotine n=24 Participants In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
Age, Continuous	15.3 years STANDARD_DEVIATION 1.3 • n=5 Participants
Age, Customized 13 years	2 Participants n=5 Participants
Age, Customized 14 years	6 Participants n=5 Participants
Age, Customized 15 years	6 Participants n=5 Participants
Age, Customized 16 years	4 Participants n=5 Participants
Age, Customized 17 years	6 Participants n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Height	167.39 cm STANDARD_DEVIATION 6.89 • n=5 Participants
Weight	65.70 kg STANDARD_DEVIATION 10.72 • n=5 Participants
BMI (Body Mass Index)	23.388 kg/m^2 STANDARD_DEVIATION 3.133 • n=5 Participants

PRIMARY outcome

Timeframe: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

Population: The Pharmacokinetic Per Protocol Set (PKPPS) includes all enrolled subjects who were included in the Safety Set, who had no protocol deviations that were considered to impact the subject's validity for analysis of the primary study objective and who for at least 1 dose step fulfilled specific predefined conditions.

CL/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma.

For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.

Outcome measures

Measure	Rotigotine (PKPPS) n=6 Participants In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 0.5 mg/24 h (2.5 cm^2)	676.86 L/h (liter per hour) Interval 408.5 to 1121.51

PRIMARY outcome

Timeframe: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

Population: The Pharmacokinetic Per Protocol Set (PKPPS) includes all enrolled subjects who were included in the Safety Set, who had no protocol deviations that were considered to impact the subject's validity for analysis of the primary study objective and who for at least 1 dose step fulfilled specific predefined conditions.

CL/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma.

For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.

Outcome measures

Measure	Rotigotine (PKPPS) n=10 Participants In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 1 mg/24 h (5 cm^2)	671.72 L/h (Liter per hour) Interval 459.11 to 982.8

PRIMARY outcome

Timeframe: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

Population: The Pharmacokinetic Per Protocol Set (PKPPS) includes all enrolled subjects who were included in the Safety Set, who had no protocol deviations that were considered to impact the subject's validity for analysis of the primary study objective and who for at least 1 dose step fulfilled specific predefined conditions.

CL/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma.

For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.

Outcome measures

Measure	Rotigotine (PKPPS) n=11 Participants In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 2 mg/24 h (10 cm^2)	937.56 L/h (Liter per hour) Interval 658.5 to 1334.89

PRIMARY outcome

Timeframe: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

Population: The Pharmacokinetic Per Protocol Set (PKPPS) includes all enrolled subjects who were included in the Safety Set, who had no protocol deviations that were considered to impact the subject's validity for analysis of the primary study objective and who for at least 1 dose step fulfilled specific predefined conditions.

CL/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma.

For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.

Outcome measures

Measure	Rotigotine (PKPPS) n=9 Participants In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
Apparent Total Body Clearance (Cl/f) of Unconjugated Rotigotine 3 mg/24 h (15 cm^2)	1088.77 L/h (Liter per hour) Interval 723.47 to 1638.53

PRIMARY outcome

Timeframe: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

Population: The Pharmacokinetic Per Protocol Set (PKPPS) includes all enrolled subjects who were included in the Safety Set, who had no protocol deviations that were considered to impact the subject's validity for analysis of the primary study objective and who for at least 1 dose step fulfilled specific predefined conditions.

VSS/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma.

For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.

Outcome measures

Measure	Rotigotine (PKPPS) n=6 Participants In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 0.5 mg/24 h (2.5 cm^2)	5403.16 L (Liter) Interval 2850.67 to 10241.17

PRIMARY outcome

Timeframe: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

Population: The Pharmacokinetic Per Protocol Set (PKPPS) includes all enrolled subjects who were included in the Safety Set, who had no protocol deviations that were considered to impact the subject's validity for analysis of the primary study objective and who for at least 1 dose step fulfilled specific predefined conditions.

VSS/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma.

For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.

Outcome measures

Measure	Rotigotine (PKPPS) n=10 Participants In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 1 mg/24 h (5 cm^2)	6220.79 L (Liter) Interval 3842.05 to 10072.28

PRIMARY outcome

Timeframe: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

Population: The Pharmacokinetic Per Protocol Set (PKPPS) includes all enrolled subjects who were included in the Safety Set, who had no protocol deviations that were considered to impact the subject's validity for analysis of the primary study objective and who for at least 1 dose step fulfilled specific predefined conditions.

VSS/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma.

For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.

Outcome measures

Measure	Rotigotine (PKPPS) n=11 Participants In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 2 mg/24 h (10 cm^2)	7114.01 L (Liter) Interval 4547.88 to 11128.07

PRIMARY outcome

Timeframe: 0 h (predose), 1 h, 2 h, 7-12 h and 22-24 h on Day 7, 14, 21 and 28

Population: The Pharmacokinetic Per Protocol Set (PKPPS) includes all enrolled subjects who were included in the Safety Set, who had no protocol deviations that were considered to impact the subject's validity for analysis of the primary study objective and who for at least 1 dose step fulfilled specific predefined conditions.

VSS/f was calculated for each subject treated with rotigotine derived from the concentrations of unconjugated rotigotine measured in plasma.

For the primary variables the parametric point estimator for each dose step and the 95% CI was calculated using the least-squares (LS) means and the root mean square of error from the ANOVA of the log-transformed data with subsequent exponential transformation.

Outcome measures

Measure	Rotigotine (PKPPS) n=9 Participants In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
Volume of Distribution at Steady State (VSS/f) of Unconjugated Rotigotine 3 mg/24 h (15 cm^2)	6037.92 L (Liter) Interval 3598.36 to 10131.41

Adverse Events

Rotigotine

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Rotigotine n=24 participants at risk In the Titration Period a subject received the first dose of rotigotine then the dose was increased weekly by a dose step over 4 weeks.
Gastrointestinal disorders Diarrhoea	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Gastrointestinal disorders Nausea	29.2% 7/24 • Number of events 11 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Gastrointestinal disorders Vomiting	8.3% 2/24 • Number of events 2 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
General disorders Application site pruritus	16.7% 4/24 • Number of events 4 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
General disorders Application site irritation	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
General disorders Irritability	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Immune system disorders Allergy to arthropod sting	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Immune system disorders Food allergy	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Infections and infestations Cellulitis	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Infections and infestations Fungal infection	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Infections and infestations Influenza	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Infections and infestations Nasopharyngitis	8.3% 2/24 • Number of events 3 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Infections and infestations Pharyngitis	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Infections and infestations Upper respiratory tract infection	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Injury, poisoning and procedural complications Stress fracture	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Injury, poisoning and procedural complications Animal bite	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Injury, poisoning and procedural complications Road traffic accident	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Injury, poisoning and procedural complications Wound	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Investigations Blood bilirubin increased	8.3% 2/24 • Number of events 2 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Metabolism and nutrition disorders Anorexia	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Metabolism and nutrition disorders Increased appetite	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Musculoskeletal and connective tissue disorders Arthralgia	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Musculoskeletal and connective tissue disorders Muscular weakness	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Musculoskeletal and connective tissue disorders Muscukoseletal pain	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Musculoskeletal and connective tissue disorders Neck pain	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Musculoskeletal and connective tissue disorders Pain in extremity	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Nervous system disorders Somnolence	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Nervous system disorders Syncope	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Nervous system disorders Headache	8.3% 2/24 • Number of events 2 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Nervous system disorders Migraine	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Nervous system disorders Dizzines	8.3% 2/24 • Number of events 2 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Nervous system disorders Sudden onset of sleep	4.2% 1/24 • Number of events 2 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Reproductive system and breast disorders Dysmenorrhoea	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Skin and subcutaneous tissue disorders Acne	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).
Skin and subcutaneous tissue disorders Urticaria	4.2% 1/24 • Number of events 1 • This summary includes TEAEs from the Titration period, Taper period and Safety Follow-up (Day 1 up to 69 days).

Additional Information

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Phone: +1877-822

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60