Down Syndrome
Conditions
Brief summary
This is a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter study of the safety and PK of ELND005 administered orally for 4 weeks. This study will enroll Down Syndrome patients 18 to 45 years of age (inclusive) without dementia.
Interventions
DRUGELND005
DRUGPlacebo
Sponsors
Elan Pharmaceuticals
OPKO Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* 18 - 45 years of age * Has an IQ of \> 40 (K-BIT) * Able and willing to have a brain MRI
Exclusion criteria
* Symptoms of dementia or worsening cognition over the past year. * Has a history of hepatitis B, hepatitis C, or HIV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (TEAEs) | 4 weeks | For all AE summaries, if a patient had more than one AE within a preferred term, the patient was counted only once, at the maximum severity and with the closest relationship to study drug. If a patient had more than one AE within a SOC, the subject was similarly counted only once when reporting results for that SOC. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline in Abnormal Neurological Examination Results | Baseline and 4 weeks | Subjects with Abnormal Neurological Examination Results |
| Pharmacokinetic Assessment | Baseline and 4 Weeks | Mean Plasma ELND005 Concentrations- Cmax |
| Cognitive Outcome (RADD Total Score) | Baseline and 4 Weeks | Rapid Assessment for Development Disabilities (RADD) The RADD test was developed from the low-difficulty items from published intelligence tests (Walsh et al 2007). It was specifically developed for evaluation of individuals with intellectual disabilities and developmental disabilities. It is a validated and reliable cognitive screening instrument that can be rapidly administered. The RADD is composed of 76 items. Each item is scored as 0 (incorrect) or 1 (correct).The test assesses a wide range of functional abilities including receptive and expressive language, orientation, registration, recall, attention, self identification, motor skills, imitation, abstract reasoning, number skills, comprehension and short-term memory to give a total score. Scores are from 0 to 76. A higher total score is correlated with a higher Cognitive Impairment level. |
| Improvement in NPI Total Scores in Subjects With NPI Score ≥1 at Baseline Baseline | Baseline and 4 weeks | The Neuropsychiatric Inventory(NPI) (Cummings et al 1994) is a behavioral measure that assesses psychopathology in dementia patients. The NPI was administered at the Baseline Visit (Day 1) and at Day 28 (EOS) or ET. A decrease in score shows an improvement in symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ELND005 BID ELND005 250 mg BID
ELND005 | 12 |
| ELND005 QD ELND005 250 mg QD
ELND005 | 5 |
| Placebo Placebo BID
Placebo | 6 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | ELND005 BID | ELND005 QD | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 26.3 years STANDARD_DEVIATION 7.43 | 27.8 years STANDARD_DEVIATION 4.03 | 30.0 years STANDARD_DEVIATION 5.93 | 27.6 years STANDARD_DEVIATION 6.49 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 5 Participants | 5 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| IQ Score | 50.6 units on a scale STANDARD_DEVIATION 13.81 | 63.3 units on a scale STANDARD_DEVIATION 19.62 | 55.8 units on a scale STANDARD_DEVIATION 6.65 | 54.3 units on a scale STANDARD_DEVIATION 13.75 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 4 Participants | 6 Participants | 20 Participants |
| Region of Enrollment United States | 12 participants | 5 participants | 6 participants | 23 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 9 Participants | 2 Participants | 3 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 12 | 2 / 5 | 0 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 5 | 0 / 6 |
Outcome results
Primary
Incidence of Adverse Events (TEAEs)
For all AE summaries, if a patient had more than one AE within a preferred term, the patient was counted only once, at the maximum severity and with the closest relationship to study drug. If a patient had more than one AE within a SOC, the subject was similarly counted only once when reporting results for that SOC.
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ELND005 BID | Incidence of Adverse Events (TEAEs) | 5 participants |
| ELND005 QD | Incidence of Adverse Events (TEAEs) | 2 participants |
| Placebo | Incidence of Adverse Events (TEAEs) | 0 participants |
Other Pre-specified
Changes From Baseline in Abnormal Neurological Examination Results
Subjects with Abnormal Neurological Examination Results
Time frame: Baseline and 4 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ELND005 BID | Changes From Baseline in Abnormal Neurological Examination Results | Baseline | 4 participants |
| ELND005 BID | Changes From Baseline in Abnormal Neurological Examination Results | Week 4 | 4 participants |
| ELND005 QD | Changes From Baseline in Abnormal Neurological Examination Results | Baseline | 1 participants |
| ELND005 QD | Changes From Baseline in Abnormal Neurological Examination Results | Week 4 | 1 participants |
| Placebo | Changes From Baseline in Abnormal Neurological Examination Results | Baseline | 3 participants |
| Placebo | Changes From Baseline in Abnormal Neurological Examination Results | Week 4 | 3 participants |
Other Pre-specified
Cognitive Outcome (RADD Total Score)
Rapid Assessment for Development Disabilities (RADD) The RADD test was developed from the low-difficulty items from published intelligence tests (Walsh et al 2007). It was specifically developed for evaluation of individuals with intellectual disabilities and developmental disabilities. It is a validated and reliable cognitive screening instrument that can be rapidly administered. The RADD is composed of 76 items. Each item is scored as 0 (incorrect) or 1 (correct).The test assesses a wide range of functional abilities including receptive and expressive language, orientation, registration, recall, attention, self identification, motor skills, imitation, abstract reasoning, number skills, comprehension and short-term memory to give a total score. Scores are from 0 to 76. A higher total score is correlated with a higher Cognitive Impairment level.
Time frame: Baseline and 4 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ELND005 BID | Cognitive Outcome (RADD Total Score) | Day 0 | 58.7 units on a scale | Standard Deviation 10.2 |
| ELND005 BID | Cognitive Outcome (RADD Total Score) | Week 4 | 59.1 units on a scale | Standard Deviation 11.5 |
| ELND005 QD | Cognitive Outcome (RADD Total Score) | Day 0 | 58.0 units on a scale | Standard Deviation 15.6 |
| ELND005 QD | Cognitive Outcome (RADD Total Score) | Week 4 | 64.3 units on a scale | Standard Deviation 13.5 |
| Placebo | Cognitive Outcome (RADD Total Score) | Day 0 | 62.2 units on a scale | Standard Deviation 9.8 |
| Placebo | Cognitive Outcome (RADD Total Score) | Week 4 | 62.8 units on a scale | Standard Deviation 10.3 |
Other Pre-specified
Improvement in NPI Total Scores in Subjects With NPI Score ≥1 at Baseline Baseline
The Neuropsychiatric Inventory(NPI) (Cummings et al 1994) is a behavioral measure that assesses psychopathology in dementia patients. The NPI was administered at the Baseline Visit (Day 1) and at Day 28 (EOS) or ET. A decrease in score shows an improvement in symptoms.
Time frame: Baseline and 4 weeks
Population: Subjects with NPI Score ≥1 at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ELND005 BID | Improvement in NPI Total Scores in Subjects With NPI Score ≥1 at Baseline Baseline | 7 participants |
| ELND005 QD | Improvement in NPI Total Scores in Subjects With NPI Score ≥1 at Baseline Baseline | 0 participants |
| Placebo | Improvement in NPI Total Scores in Subjects With NPI Score ≥1 at Baseline Baseline | 1 participants |
Other Pre-specified
Pharmacokinetic Assessment
Mean Plasma ELND005 Concentrations- Cmax
Time frame: Baseline and 4 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ELND005 BID | Pharmacokinetic Assessment | Mean Cmax, First Dose, Day 0 | 1.68 μg/mL | Standard Deviation 0.9 |
| ELND005 BID | Pharmacokinetic Assessment | Mean Cmax, Last Dose, Day 28 | 6.33 μg/mL | Standard Deviation 1.95 |
| ELND005 QD | Pharmacokinetic Assessment | Mean Cmax, First Dose, Day 0 | 2.61 μg/mL | Standard Deviation 0.62 |
| ELND005 QD | Pharmacokinetic Assessment | Mean Cmax, Last Dose, Day 28 | 4.48 μg/mL | Standard Deviation 1.13 |
| Placebo | Pharmacokinetic Assessment | Mean Cmax, First Dose, Day 0 | 0 μg/mL | Standard Deviation 0 |
| Placebo | Pharmacokinetic Assessment | Mean Cmax, Last Dose, Day 28 | 0 μg/mL | Standard Deviation 0 |