Trial Outcomes & Findings for Rivastigmine Study in Adolescents With Down Syndrome (NCT NCT01084135)
NCT ID: NCT01084135
Last Updated: 2015-04-06
Results Overview
The Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) is a measure of adaptive behavior in children, adolescents and adults. It yields an overall standard score (Adaptive Behavior Composite, ABC) and age standard scores in four domains. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160). Higher scores suggest a higher level of adaptive functioning. In this study, the change between each subject's ABC at Baseline and the Final Visit was computed. A rise in standard scores from Baseline to the Final Visit indicates improvement.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
42 participants
Primary outcome timeframe
Baseline & Study termination (Week 20)
Results posted on
2015-04-06
Participant Flow
8 participant started and completed the 12 week period. The protocol was amended and 23 subject enrolled into the 20 week amended period (22 completed).
42 subjects signed consent, 10 were screen failures, 1 withdrew consent prior to being assigned to an arm, 1 was withdrawn by PI after being assigned an arm for noncompliance, 30 completed study.
Participant milestones
| Measure |
Rivastigmine- Liquid Form
At the baseline visit (week 0), the subject will begin rivastigmine treatment at a dose of 0.75 mg bid. This dose will be continued for two weeks and then increased to 1.5 mg bid for an additional eight weeks. At the week 10 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 10 weeks. If a subject is unable to tolerate a particular dose, the dose will be lowered to the previously tolerated dose, down to a minimum of 0.75 mg bid. If the subject is unable to tolerate the 0.75 mg bid dose he/she will be dismissed from the study.
|
Liquid Placebo
Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
Liquid Placebo: Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
|
|---|---|---|
|
12 Week
STARTED
|
4
|
4
|
|
12 Week
COMPLETED
|
4
|
4
|
|
12 Week
NOT COMPLETED
|
0
|
0
|
|
20 Week
STARTED
|
12
|
11
|
|
20 Week
COMPLETED
|
12
|
10
|
|
20 Week
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Rivastigmine- Liquid Form
At the baseline visit (week 0), the subject will begin rivastigmine treatment at a dose of 0.75 mg bid. This dose will be continued for two weeks and then increased to 1.5 mg bid for an additional eight weeks. At the week 10 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 10 weeks. If a subject is unable to tolerate a particular dose, the dose will be lowered to the previously tolerated dose, down to a minimum of 0.75 mg bid. If the subject is unable to tolerate the 0.75 mg bid dose he/she will be dismissed from the study.
|
Liquid Placebo
Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
Liquid Placebo: Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
|
|---|---|---|
|
20 Week
Physician Decision
|
0
|
1
|
Baseline Characteristics
Rivastigmine Study in Adolescents With Down Syndrome
Baseline characteristics by cohort
| Measure |
20 Week Rivastigmine- Liquid Form
n=12 Participants
At the baseline visit (week 0), the subject will begin rivastigmine treatment at a dose of 0.75 mg bid. This dose will be continued for two weeks and then increased to 1.5 mg bid for an additional eight weeks. At the week 10 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 10 weeks. If a subject is unable to tolerate a particular dose, the dose will be lowered to the previously tolerated dose, down to a minimum of 0.75 mg bid. If the subject is unable to tolerate the 0.75 mg bid dose he/she will be dismissed from the study.
|
20 Week Liquid Placebo
n=11 Participants
Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
Liquid Placebo: Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
|
12 Week Rivastigmine- Liquid Form
n=4 Participants
At the baseline visit (week 0), the subject will begin rivastigmine treatment at a dose of 0.75 mg bid. This dose will be continued for two weeks and then increased to 1.5 mg bid for an additional four weeks. At the week 6 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 6 weeks.
|
12 Week Liquid Placebo
n=4 Participants
Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
Liquid Placebo: Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
|
Total
n=31 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
12 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
31 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
11 participants
n=7 Participants
|
4 participants
n=5 Participants
|
4 participants
n=4 Participants
|
31 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline & Study termination (Week 20)Population: All subjects who completed the 20 week period were included in analysis except for 2 subjects whose form was completed incorrectly.
The Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) is a measure of adaptive behavior in children, adolescents and adults. It yields an overall standard score (Adaptive Behavior Composite, ABC) and age standard scores in four domains. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160). Higher scores suggest a higher level of adaptive functioning. In this study, the change between each subject's ABC at Baseline and the Final Visit was computed. A rise in standard scores from Baseline to the Final Visit indicates improvement.
Outcome measures
| Measure |
Rivastigmine- Liquid Form
n=10 Participants
At the baseline visit (week 0), the subject will begin rivastigmine treatment at a dose of 0.75 mg bid. This dose will be continued for two weeks and then increased to 1.5 mg bid for an additional eight weeks. At the week 10 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 10 weeks. If a subject is unable to tolerate a particular dose, the dose will be lowered to the previously tolerated dose, down to a minimum of 0.75 mg bid. If the subject is unable to tolerate the 0.75 mg bid dose he/she will be dismissed from the study.
|
Liquid Placebo
n=10 Participants
Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
Liquid Placebo: Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
|
|---|---|---|
|
Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form)
|
-1.7 units on a scale
Standard Deviation 3.2
|
2.0 units on a scale
Standard Deviation 3.6
|
SECONDARY outcome
Timeframe: Baseline and Final (Week 20) visitPopulation: All subjects who completed the 20 week period were included in analysis except for 1 subjects whose form was completed incorrectly.
The Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) is a parent report measure of executive function behaviors in children in their home setting. It yields an overall score (Global Executive Composite, GEC) that is based on its five clinical scales. Raw scores range from 63 to 189. Higher scores suggest that an individual's executive function skills are more problematic. In this study, the change between each subject's raw score at Baseline and the Final Visit was computed for the Global Executive Composite. A decline in raw scores from Baseline to the Final Visit indicates improvement.
Outcome measures
| Measure |
Rivastigmine- Liquid Form
n=11 Participants
At the baseline visit (week 0), the subject will begin rivastigmine treatment at a dose of 0.75 mg bid. This dose will be continued for two weeks and then increased to 1.5 mg bid for an additional eight weeks. At the week 10 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 10 weeks. If a subject is unable to tolerate a particular dose, the dose will be lowered to the previously tolerated dose, down to a minimum of 0.75 mg bid. If the subject is unable to tolerate the 0.75 mg bid dose he/she will be dismissed from the study.
|
Liquid Placebo
n=10 Participants
Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
Liquid Placebo: Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
|
|---|---|---|
|
Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P)
|
-3.6 units on a scale
Standard Deviation 7.7
|
-6.1 units on a scale
Standard Deviation 12.0
|
Adverse Events
20 Week: Rivastigmine- Liquid Form
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
20 Week: Liquid Placebo
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
12 Week: Rivastigmine- Liquid Form
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
12 Week: Liquid Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
20 Week: Rivastigmine- Liquid Form
n=12 participants at risk
At the baseline visit (week 0), the subject will begin rivastigmine treatment at a dose of 0.75 mg bid. This dose will be continued for two weeks and then increased to 1.5 mg bid for an additional eight weeks. At the week 10 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 10 weeks. If a subject is unable to tolerate a particular dose, the dose will be lowered to the previously tolerated dose, down to a minimum of 0.75 mg bid. If the subject is unable to tolerate the 0.75 mg bid dose he/she will be dismissed from the study.
|
20 Week: Liquid Placebo
n=11 participants at risk
Liquid Placebo: Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
|
12 Week: Rivastigmine- Liquid Form
n=4 participants at risk
At the baseline visit (week 0), the subject will begin rivastigmine treatment at a dose of 0.75 mg bid. This dose will be continued for two weeks and then increased to 1.5 mg bid for an additional four weeks. At the week 6 safety visit, the dose will be increased to 4.5 mg/day (3.0 mg and 1.5 mg) for an additional 6 weeks.
|
12 Week: Liquid Placebo
n=4 participants at risk
Liquid Placebo: Subjects receiving placebo will maintain matched titration volume increase as treatment arm. The placebo will be matched to liquid rivastigmine in consistency and taste.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
3/12
|
18.2%
2/11
|
0.00%
0/4
|
75.0%
3/4
|
|
Gastrointestinal disorders
Nausea
|
25.0%
3/12
|
27.3%
3/11
|
25.0%
1/4
|
25.0%
1/4
|
|
Gastrointestinal disorders
Stomach ache
|
41.7%
5/12
|
27.3%
3/11
|
0.00%
0/4
|
25.0%
1/4
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
3/12
|
9.1%
1/11
|
25.0%
1/4
|
50.0%
2/4
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
50.0%
2/4
|
|
Nervous system disorders
Headache
|
8.3%
1/12
|
9.1%
1/11
|
25.0%
1/4
|
0.00%
0/4
|
|
Nervous system disorders
Trouble sleeping
|
8.3%
1/12
|
9.1%
1/11
|
0.00%
0/4
|
50.0%
2/4
|
|
Metabolism and nutrition disorders
Decreased appetite
|
8.3%
1/12
|
9.1%
1/11
|
25.0%
1/4
|
25.0%
1/4
|
|
Nervous system disorders
Shakiness
|
0.00%
0/12
|
9.1%
1/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Weakness
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Blood and lymphatic system disorders
Lumps in neck
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Skin and subcutaneous tissue disorders
Boil
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Reproductive system and breast disorders
Menstural cramps
|
16.7%
2/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Injury, poisoning and procedural complications
Cut
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Nervous system disorders
Restless legs
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Skin and subcutaneous tissue disorders
Pale coloring
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Nervous system disorders
Foot twitching
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Skin and subcutaneous tissue disorders
Itchy
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Eye disorders
Eye twitch
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Hepatobiliary disorders
Increased bilirubin
|
0.00%
0/12
|
9.1%
1/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Gastrointestinal disorders
Indigestion
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Gastrointestinal disorders
Constipation
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Skin and subcutaneous tissue disorders
Worsening acne
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
General disorders
Cold
|
25.0%
3/12
|
18.2%
2/11
|
0.00%
0/4
|
0.00%
0/4
|
|
General disorders
Stomach flu
|
16.7%
2/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
General disorders
Fever
|
0.00%
0/12
|
18.2%
2/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Skin and subcutaneous tissue disorders
Worsening alopecia
|
0.00%
0/12
|
9.1%
1/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Leg cramps
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Renal and urinary disorders
Incontinence
|
8.3%
1/12
|
9.1%
1/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Psychiatric disorders
Assertive, stubborn, more emotional
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Nervous system disorders
Fainted
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Gastrointestinal disorders
Sleepy
|
16.7%
2/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
General disorders
Fatigue
|
8.3%
1/12
|
0.00%
0/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Renal and urinary disorders
Frequent urination
|
0.00%
0/12
|
9.1%
1/11
|
25.0%
1/4
|
0.00%
0/4
|
|
Metabolism and nutrition disorders
Weight gain
|
0.00%
0/12
|
9.1%
1/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Gastrointestinal disorders
excessive gas
|
0.00%
0/12
|
0.00%
0/11
|
25.0%
1/4
|
0.00%
0/4
|
|
Psychiatric disorders
behavior problems
|
0.00%
0/12
|
0.00%
0/11
|
75.0%
3/4
|
25.0%
1/4
|
|
Infections and infestations
Vaginal yeast infection
|
0.00%
0/12
|
9.1%
1/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Renal and urinary disorders
Urinary track infection
|
0.00%
0/12
|
9.1%
1/11
|
0.00%
0/4
|
0.00%
0/4
|
|
Psychiatric disorders
nightmares
|
0.00%
0/12
|
0.00%
0/11
|
25.0%
1/4
|
0.00%
0/4
|
|
Skin and subcutaneous tissue disorders
acne
|
0.00%
0/12
|
0.00%
0/11
|
0.00%
0/4
|
25.0%
1/4
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place