Clinical Trial Results:
An Open-Label 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).
Summary
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EudraCT number |
2012-001616-33 |
Trial protocol |
GB HU BE ES NL EE IS IT |
Global end of trial date |
09 Jul 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Aug 2018
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First version publication date |
10 Aug 2018
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Other versions |
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-91
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01592786 | ||
WHO universal trial number (UTN) |
- | ||
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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Aug 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Jul 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Jul 2013
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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 |
The objective of this study is to evaluate the safety and tolerability of memantine in pediatric (6-12 years old) patients with autism, Asperger’s Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and to identify responders for participation in the follow-up randomized withdrawal study
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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 |
01 Jun 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Belgium: 11
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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 |
Estonia: 6
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Country: Number of subjects enrolled |
France: 14
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Country: Number of subjects enrolled |
Hungary: 20
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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 |
Korea, Republic of: 25
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Country: Number of subjects enrolled |
New Zealand: 2
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Country: Number of subjects enrolled |
Poland: 37
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Country: Number of subjects enrolled |
Serbia: 21
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Country: Number of subjects enrolled |
Singapore: 1
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Country: Number of subjects enrolled |
South Africa: 2
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Country: Number of subjects enrolled |
Spain: 17
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Country: Number of subjects enrolled |
Ukraine: 16
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Country: Number of subjects enrolled |
United States: 714
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Worldwide total number of subjects |
906
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EEA total number of subjects |
116
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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) |
793
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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 June of 2011 to May of 2012, at 118 study sites, located in the Untied States and 17 other countries. Australia: Belgium: Canada: Colombia Estonia: France: Hungary: Iceland: Italy: New Zealand: Poland: Singapore: South Africa: South Korea Spain: Ukraine | ||||||||||||||||||||
Pre-assignment
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Screening details |
Enrolled patients went through a 2-week screening period. | ||||||||||||||||||||
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 | ||||||||||||||||||||
Arms
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Arm title
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Memantine Hydrochloride (HCl) ER | ||||||||||||||||||||
Arm description |
Memantine Hydrochloride (HCl) extended-release 3-mg capsules once daily, oral administration. 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 |
Ebixa, Namenda, Axura, Akatinol, Abixa, Memox
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Memantine Hydrochloride (HCl) extended-release 3-mg capsules once daily, oral administration. Dosing
was 3-mg, 6-mg, 9-mg, 12-mg, or 15-mg per day, based upon patient weight.
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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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Subject analysis sets
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Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Of the 906 patients who enrolled in the study 903 received at least 1 dose of open-label treatment to comprise the Safety Population.
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Subject analysis set title |
Intent to Treat Population
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The Intent to Treat (ITT) population included the 868 patients in the Safety population who also had at least 1 post–Visit 1 assessment of the SRS total raw score.
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End points reporting groups
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Reporting group title |
Memantine Hydrochloride (HCl) ER
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Reporting group description |
Memantine Hydrochloride (HCl) extended-release 3-mg capsules once daily, oral administration. Dosing was 3-mg, 6-mg, 9-mg, 12-mg, or 15-mg per day, based upon patient weight. | ||
Subject analysis set title |
Safety Population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Of the 906 patients who enrolled in the study 903 received at least 1 dose of open-label treatment to comprise the Safety Population.
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Subject analysis set title |
Intent to Treat Population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The Intent to Treat (ITT) population included the 868 patients in the Safety population who also had at least 1 post–Visit 1 assessment of the SRS total raw score.
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End point title |
Number of Social Responsiveness Scale (SRS) Confirmed Responders [1] | ||||||||||
End point description |
A confirmed SRS responder was defined as a patient who had at least 12 weeks of exposure to memantine, and a ≥ 10-point reduction in the SRS total raw score relative to baseline at 2 consecutive visits separated by at least 2 weeks. The SRS is a 65-item, caregiver-rated assessment scale that measures observable items on social behavior and social language use, as well as characteristics of autism in a naturalistic social setting. Each item is rated on a scale from 0 (never true) to 3 (almost always true). The SRS total raw score ranges from 0 to 195; a higher score indicates greater severity of social impairment.
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End point type |
Primary
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End point timeframe |
Visit 1 (Baseline) to Visit 8 (week 48/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: No inferential statistical analyses were performed for the efficacy parameters. |
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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 over a 14 month period from June 2012 to August 2013 at 118 study sites in the US and 17 other countries.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. 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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25 Mar 2013 |
Amendment #1 specifies the following changes to the original protocol MEM-MD-91, dated April 05, 2012:
Increasing sample size from approximately 192 enrolled patients to approximately 800 to 900 enrolled patients.
Rationale: The Number of Patients (Planned and Analyzed) section has been amended to change the planned sample size such that a sufficient number of patients can be enrolled in MEM-MD-68 from this lead-in study. The sample size of MEM-MD-68 has been increased based on the discussion with the FDA. In order to provide sufficient patients transitioning to a follow-up randomized withdrawal study (MEM-MD-68), approximately 800 to 900 patients will be enrolled into this study.
Adding information regarding the Data Safety Monitoring Board (DSMB)
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.
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 was revised to clarify if administration of the C-SSRS is appropriate given a patient’s developmental and/or situational status.
All references to the Social Responsiveness Scale (SRS) Patient Autoscore version have been revised.
Rational: The Social Responsiveness Scale (SRS) Patient Autoscore version has not been provided to the sites. The SRS total raw score should be calculated before the patient/caregiver leave the site.
Immediate Reporting of Serious Adverse Events
Rationale: This section was revised to indicate where the SAE Form fax number and Medical Emergency phone number for sites outside the United States and Canada can be found.
Contact Information
Rationale: Appendix II was revised to indicate where the contact information and Medical Emergency phone number for sites outside the United States and Canada can be found. |
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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 |