Clinical Trial Results:
An Open-Label Extension Study of the Safety and Tolerability of Memantine in Pediatric Patients with Autism, Asperger’s Disorder or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)
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Summary
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EudraCT number |
2012-001630-33 |
Trial protocol |
GB HU BE ES NL EE FR IS IT |
Global end of trial date |
31 Jan 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Aug 2018
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First version publication date |
09 Aug 2018
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MEM-MD-69
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01592773 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Forest Laboratories LLC, a subsidiary of Allergan, plc
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Sponsor organisation address |
1 Grand Canal Square, Docklands, Ireland, Dublin 2
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Public contact |
Clinical Trial Information Desk, Forest Laboratories LLC, a subsidiary of Allergan, plc,, 001 866-369-5227 ,
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Scientific contact |
Joel Trugman, Forest Laboratories LLC, a subsidiary of Allergan, plc,, 001 201-427-8000 , Joel.Trugman@actavis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Mar 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jan 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jan 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the long-term safety and tolerability of memantine in the treatment of pediatric patients with autism, Asperger’s Disorder or Pervasive Developmental Disorder Not Otherwise Specified
(PDD-NOS).
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Protection of trial subjects |
At each study center, the Investigator was responsible for ensuring that the investigation
was conducted according to the signed Investigator agreement, the protocol, good clinical
practice guidelines, and applicable regulations; for protecting the rights, safety, and
welfare of patients under the Investigator’s care; and for the control of investigational
products under investigation. The Investigator at each study center was responsible for
the management of the study, which consisted of maintaining the study file and patient
records, corresponding with the IRB/IEC, and completing the electronic case report
forms (eCRFs).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Apr 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 36
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Country: Number of subjects enrolled |
Spain: 14
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Country: Number of subjects enrolled |
Belgium: 4
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Country: Number of subjects enrolled |
Estonia: 5
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Country: Number of subjects enrolled |
France: 9
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Country: Number of subjects enrolled |
Hungary: 14
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Country: Number of subjects enrolled |
Iceland: 5
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Country: Number of subjects enrolled |
Italy: 6
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Country: Number of subjects enrolled |
United States: 586
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Colombia: 8
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Country: Number of subjects enrolled |
Korea, Republic of: 22
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Country: Number of subjects enrolled |
New Zealand: 1
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Country: Number of subjects enrolled |
Serbia: 21
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Country: Number of subjects enrolled |
South Africa: 1
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Country: Number of subjects enrolled |
Ukraine: 14
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Worldwide total number of subjects |
747
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EEA total number of subjects |
93
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
634
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Adolescents (12-17 years) |
113
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Patient recruitment occurred over an eleven month period, from October of 2012 to September of 2013, at 106 study sites, located in the United States and 15 other countries. | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Patients who took open-label memantine in the preceding study, MEM-MD-67 orMEM-MD-91, will receive 48 weeks of open-label memantine at their maximum tolerated weight-based target dosage. Patients who participated in the double-blind study MEM-MD-68 will undergo 6 weeks of double-blind dosing followed by 42 weeks of open-label dosing. During the | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||
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Arms
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Arm title
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Memantine Hydrochloride (HCl) | ||||||||||||||||||||||||
Arm description |
Memantine Hydrochloride (HCl) extended-release 3-mg capsules once daily, oral administration.... more Dosing was 3-mg, 6-mg, 9-mg, 12-mg, or 15-mg per day, based upon patient weight. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Memantine
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Investigational medicinal product code |
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Other name |
Namenda, Axura, Akatinol, Ebixa, Abixa, Memox
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Memantine extended-release 3mg capsules; oral administration. The maximum target dosage was identified during the prior studies for each patient. Dosing was once daily.
The weight-based dose limits in this study were as follows:
Group A: ≥ 60 kg; maximum 15 mg/day Group B: 40-59 kg; maximum 9 mg/day Group C: 20-39 kg; maximum 6 mg/day Group D: < 20 kg; maximum 3 mg/day
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
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End points reporting groups
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Reporting group title |
Memantine Hydrochloride (HCl)
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Reporting group description |
Memantine Hydrochloride (HCl) extended-release 3-mg capsules once daily, oral administration.... more Dosing was 3-mg, 6-mg, 9-mg, 12-mg, or 15-mg per day, based upon patient weight. | ||
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End point title |
Patients With Any Treatment-emergent Adverse Event [1] | ||||||
End point description |
Number of patients who experienced 1 or more Treatment Emergent Adverse Event
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End point type |
Primary
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End point timeframe |
Visit 1 (Week 0) up to 30 days after Visit 8 (up to Week 48) or Final Visit
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This was an exploratory study with an emphasis on safety. |
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| Notes [2] - Analysis was performed on the 747 patients who took at least 1 dose of investigational product (Safe |
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse Event data was collected from study participants for 48 weeks at 106 sites in the US and 15 other countries.
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Adverse event reporting additional description |
Safety results are based on the safety population (ie, all patients who took at least one dose of investigational product).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
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Reporting groups
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Reporting group title |
Memantine Hydrochloride (HCl)
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Reporting group description |
Memantine Hydrochloride (HCl) extended-release 3-mg capsules once daily, oral administration.... more Dosing was 3-mg, 6-mg, 9-mg, 12-mg, or 15-mg per day, based upon patient weight. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 Mar 2013 |
1. Increasing sample size from about 220 to about 800-900;
Rationale: The sample size has been increased based on the increased enrollment of the lead-in studies MEM-MD-91 and MEM-MD-68.
2. Clarifying if administration of the Columbia-Suicide Severity Rating Scale (C-SSRS) is appropriate given a patient’s developmental and or/situational status;
Rationale: This section has been amended to clarify if administration of the C-SSRS is
appropriate given a patient’s developmental and/or situational status.
3. Removing reference to the CGI-I being performed at Visit 1;
a. Clarify that laboratory and ECG results received after randomization should be done
with respect to the eligibility criteria;
b. Remove the Clinical Global Impression - Improvement (CGI-I) scale from the section
“If Visit 1 is being held more than 14 days after the final visit of the preceding study,
the following procedures must be performed:”
4. Adding information regarding the Data Safety Monitoring Board;
Rationale: This section has been added to include information about the DSMB. No safety issue necessitated the use of the DSMB. An Ethics Committee requested that a DSMB be established. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
