Safety Study of Memantine in Pediatric Patients With Autism, Asperger's Disorder or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01592773
• Collaborator: (none)
• Enrollment: 747
• Locations: 106
• Arm: 1
• Duration (Months): 17
• Patients Per Site: 7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The objective of this study is 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).

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorder (ASD); Autism; Autistic Disorder; Asperger's Disorder; Asperger's; Pediatric Autism; Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)	Drug: Memantine Hydrochloride (HCl)	Phase 2

Detailed Description

This clinical study was a 48-week, multicenter, multinational, open-label extension study in pediatric outpatients with autism, Asperger's Disorder, or PDD-NOS conducted at 106 study centers. Patients were eligible for this long-term extension study if they had:

• completed the open-label Study MEM MD 67,or

• completed the open-label Study MEM-MD-91, or

• completed the double-blind Study MEM-MD-68, or

• discontinued study MEM-MD-68 by meeting requirements for loss of therapeutic response

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

The decision to close the study early was based on data from 2 double-blind placebo-controlled studies (MEM-MD-57A and MEM-MD-68) that failed to demonstrate a statistically significant difference between memantine and placebo in the primary efficacy parameter based on Social Responsiveness Scale (SRS) total raw score.

Study Design

• Study Type: Interventional
• Actual Enrollment: 747 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Memantine To maintain the blind of the preceding study, patients who participated in MEM-MD-68 (NCT01592747) began this study with 6 weeks of double blind dosing during which all patients were either titrated to or remained on their maximum target dosages. This was followed by up-to 42 weeks of open-label dosing. Patients who took open-label memantine in study MEM-MD-67 (NCT01999894) or MEM-MD-91(NCT01592786), received up to 48 weeks of open-label memantine at their maximum tolerated weight based target dosage.

Drug: Memantine Hydrochloride (HCl); During the 6-week double-blind dosing titration/maintenance period, Memantine extended-release 3-mg and 6-mg capsules; oral administration. Dosing was once daily. During open-label treatment: Memantine extended-release 3mg capsules; oral administration. The maximum target dosage was identified during the prior studies for each patient. Dosing was once daily.; Other Names: Namenda

Outcome Measures

Primary Outcome Measures

1. Patients With Any Treatment-emergent Adverse Event [Visit 1 (Week 0) up to 30 days after Visit 8 (up to Week 48) or Final Visit]

   Number of patients who experienced 1 or more Treatment Emergent Adverse Event

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who completed Study MEM-MD-67, MEM-MD-68, MEM-MD-91, or discontinued Study MEM-MD-68 due to meeting the criterion for loss of therapeutic response.

• Having normal results from a physical examination and laboratory tests at Visit 1 of this study (last visit of the preceding study). Any abnormal findings must be deemed not clinically significant by the Investigator and documented as such.

• Have a family that is sufficiently organized and stable to guarantee adequate safety monitoring and continuous attendance to clinic visits for the duration of the study

Exclusion Criteria:

• Patients who discontinued a preceding memantine study due to an adverse event possibly related to study drug

• Patients with a concurrent medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger the patient's well being

• Significant risk of suicidality based on the Investigator's judgment, Aberrant Behavior Checklist-irritability subscale (ABC-I), or if appropriate, as indicated by a response of "yes" to questions 4 or 5 in the suicidal ideation section of the Children's Columbia-Suicide Severity Rating Scale (C-SSRS) or any suicidal behavior

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Forest Investigative Site 068	Dothan	Alabama	United States	36303
2	Forest Investigative Site 005	Phoenix	Arizona	United States	85006
3	Forest Investigative Site 055	Tucson	Arizona	United States	85718
4	Forest Investigative Site 077	Little Rock	Arkansas	United States	72202-3591
5	Forest Investigative Site 054	Glendale	California	United States	91206
6	Forest Investigative Site 109	Imperial	California	United States	92251
7	Forest Investigative Site 066	Irvine	California	United States	92612
8	Forest Investigative Site 096	Los Angeles	California	United States	90024
9	Forest Investigative Site 021	San Francisco	California	United States	94143-0984
10	Forest Investigative Site 026	Santa Ana	California	United States	92701
11	Forest Investigative Site 002	Stanford	California	United States	94305-5719
12	Forest Investigative Site 078	Boulder	Colorado	United States	80304
13	Forest Investigative Site 073	Centennial	Colorado	United States	80112
14	Forest Investigative Site 052	Washington	District of Columbia	United States	20010-2970
15	Forest Investigative Site 075	Bradenton	Florida	United States	32751
16	Forest Investigative Site 080	Gainesville	Florida	United States	32607
17	Forest Investigative Site 117	Jacksonville	Florida	United States	32216
18	Forest Investigative Site 065	Maitland	Florida	United States	32751
19	Forest Investigative Site 118	Miami	Florida	United States	33155
20	Forest Investigative Site 085	Oakland Park	Florida	United States	33334
21	Forest Investigative Site 115	Orange City	Florida	United States	32763
22	Forest Investigative Site 125	Orlando	Florida	United States	32803
23	Forest Investigative Site 062	Orlando	Florida	United States	32806
24	Forest Investigative Site 067	Tampa	Florida	United States	33613
25	Forest Investigative Site 101	Wellington	Florida	United States	33414
26	Forest Investigative Site 102	Libertyville	Illinois	United States	60048
27	Forest Investigative Site 023	Naperville	Illinois	United States	60563
28	Forest Investigative Site 082	Evansville	Indiana	United States	47713
29	Forest Investigative Site 123	Fort Wayne	Indiana	United States	46805
30	Forest Investigative Site 056	Indianapolis	Indiana	United States	46260
31	Forest Investigative Site 061	Louisville	Kentucky	United States	40202
32	Forest Investigative Site 095	Lake Charles	Louisiana	United States	70605
33	Forest Investigative Site 091	New Orleans	Louisiana	United States	70112
34	Forest Investigative Site 086	Rockville	Maryland	United States	20852
35	Forest Investigative Site 059	Newton	Massachusetts	United States	02459
36	Forest Investigative Site 108	Springfield	Massachusetts	United States	01199
37	Forest Investigative Site 116	Lincoln	Nebraska	United States	68516
38	Forest Investigative Site 097	Lincoln	Nebraska	United States	68526
39	Forest Investigative Site 130	Henderson	Nevada	United States	89052
40	Forest Investigative Site 104	Las Vegas	Nevada	United States	89128
41	Forest Investigative Site 136	Neptune	New Jersey	United States	07753
42	Forest Investigative Site 127	Toms River	New Jersey	United States	08755
43	Forest Investigative Site 081	Albuquerque	New Mexico	United States	87108-5129
44	Forest Investigative Site 107	Albuquerque	New Mexico	United States	87109
45	Forest Investigative Site 098	Bronx	New York	United States	10467
46	Forest Investigative Site 072	Chapel Hill	North Carolina	United States	27514
47	Forest Investigative Site 069	Avon Lake	Ohio	United States	44012
48	Forest Investigative Site 001	Columbus	Ohio	United States	43210
49	Forest Investigative Site 019	Oklahoma City	Oklahoma	United States	73116
50	Forest Investigative Site 092	Tulsa	Oklahoma	United States	74104
51	Forest Investigative Site 053	Gresham	Oregon	United States	97030
52	Forest Investigative Site 132	Johnstown	Pennsylvania	United States	15904
53	Forest Investigative Site 131	McMurray	Pennsylvania	United States	15317
54	Forest Investigative Site 100	Media	Pennsylvania	United States	19063
55	Forest Investigative Site 105	Charleston	South Carolina	United States	29407
56	Forest Investigative Site 090	Memphis	Tennessee	United States	38119
57	Forest Investigative Site 057	Nashville	Tennessee	United States	37232
58	Forest Investigative Site 051	Houston	Texas	United States	77090
59	Forest Investigative Site 070	The Woodlands	Texas	United States	77381
60	Forest Investigative Site 028	Clinton	Utah	United States	84015
61	Forest Investigative Site 141	Ogden	Utah	United States	84405
62	Forest Investigative Site 029	Salt Lake City	Utah	United States	84106
63	Forest Investigative Site 064	Charlottesville	Virginia	United States	22903
64	Forest Investigative Site 113	Norfolk	Virginia	United States	23507
65	Forest Investigative Site 124	Roanoke	Virginia	United States	24014
66	Forest Investigative Site 071	Bothell	Washington	United States	98011
67	Forest Investigative Site 119	Charleston	West Virginia	United States	25304
68	Forest Investigative Site 063	Middleton	Wisconsin	United States	53562
69	Forest Investigative Site 204	Brussels		Belgium	1020
70	Forest Investigative Site 203	Jette		Belgium	1090
71	Forest Investigative Site 155	Toronto	Ontario	Canada	M5B 1T8
72	Forest Investigative Site 228	Antioquia	Bello	Colombia
73	Forest Investigative Site 227	Barranquilla		Colombia	84176
74	Forest Investigative Site 226	Bogota		Colombia
75	Forest Investigative Site 276	Tallinn		Estonia	10617
76	Forest Investigative Site 329	Bron Cedex	Rhone	France	69500
77	Forest Investigative Site 381	Budapest		Hungary	1026
78	Forest Investigative Site 376	Budapest		Hungary	1083
79	Forest Investigative Site 378	Budapest		Hungary	1089
80	Forest Investigative Site 382	Gyula		Hungary	5700
81	Forest Investigative Site 401	Kopavogur		Iceland	200
82	Forest Investigative Site 453	Roma		Italy	00165
83	Forest Investigative Site 452	Siena		Italy	53100
84	Forest Investigative Site 704	Yangsan-si	Gyeongsangnam-do	Korea, Republic of	626-770
85	Forest Investigative Site 702	Seoul		Korea, Republic of	110744
86	Forest Investigative Site 703	Seoul		Korea, Republic of	120752
87	Forest Investigative Site 701	Seoul		Korea, Republic of	138736
88	Forest Investigative Site 526	Wellington		New Zealand	7902
89	Forest Investigative Site 579	Gdansk		Poland	80542
90	Forest Investigative Site 578	Gdansk		Poland	80952
91	Forest Investigative Site 580	Kielce		Poland	25317
92	Forest Investigative Site 576	Tyniec Maly		Poland	55040
93	Forest Investigative Site 577	Warsaw		Poland	80214
94	Forest Investigative Site 626	Belgrade		Serbia	11000
95	Forest Investigative Site 627	Belgrade		Serbia	11000
96	Forest Investigative Site 629	Nis		Serbia	18000
97	Forest Investigative Site 628	Novi Sad		Serbia	21000
98	Forest Investigative Site 676	Bellville Cape Town		South Africa	7530
99	Forest Investigative Site 729	Barcelona		Spain	08221
100	Forest Investigative Site 728	Sabadell		Spain	08208
101	Forest Investigative Site 730	Torremolinos		Spain	29620
102	Forest Investigative Site 803	Donetsk		Ukraine	83008
103	Forest Investigative Site 807	Kharkiv		Ukraine	61153
104	Forest Investigative Site 802	Kherson		Ukraine	73488
105	Forest Investigative Site 804	Kyiv		Ukraine	4080
106	Forest Investigative Site 801	Odessa		Ukraine	65014

Sponsors and Collaborators

• Forest Laboratories

Investigators

• Study Director: Jordan Lateiner, MS, MBA, Forest Research Institute, Inc.- A Subsidiary of Forest Laboratories, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT01592773
• Other Study ID Numbers: MEM-MD-69
• First Posted: May 7, 2012
• Last Update Posted: Feb 16, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by Forest Laboratories: Autistic Disorder; Asperger's Disorder; Asperger's; Pediatric Autism; Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS); Pervasive Child Development Disorder
• Additional relevant MeSH terms: Disease; Autistic Disorder; Autism Spectrum Disorder; Developmental Disabilities; Child Development Disorders, Pervasive; Asperger Syndrome; Memantine

Study Results

Participant Flow

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.

Arm/Group Title	Memantine
Arm/Group Description	To maintain the blind of the preceding study, patients who participated in MEM-MD-68 began this study with 6 weeks of double blind dosing during which all patients were either titrated to or remained on their maximum target dosages. This was followed by up-to 42 weeks of open-label dosing. Patients who took open-label memantine in the preceding study, MEM-MD-67 or MEM-MD-91, received up to 48 weeks of open-label memantine at their maximum tolerated weight based target dosage.
Period Title: Overall Study
STARTED	747
COMPLETED	81
NOT COMPLETED	666

Baseline Characteristics

Arm/Group Title	Memantine
Arm/Group Description	To maintain the blind of the preceding study, patients who participated in MEM-MD-68 began this study with 6 weeks of double blind dosing during which all patients were either titrated to or remained on their maximum target dosages. This was followed by up-to 42 weeks of open-label dosing. Patients who took open-label memantine in the preceding study, MEM-MD-67 or MEM-MD-91, received up to 48 weeks of open-label memantine at their maximum tolerated weight based target dosage.
Overall Participants	747
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.0 (1.9)
Sex: Female, Male (Count of Participants)
Female	120 16.1%
Male	627 83.9%
Race/Ethnicity, Customized (participants) [Number]
White	636 85.1%
Black or African American	42 5.6%
Asian	44 5.9%
American Indian or Alaska Native	2 0.3%
Native Hawaiian or Other Pacific Islander	3 0.4%
Other Race	20 2.7%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	88 11.8%
Not Hispanic or Latino	659 88.2%
Region of Enrollment (participants) [Number]
United States	586 78.4%
Belgium	4 0.5%
Canada	1 0.1%
Colombia	8 1.1%
Estonia	5 0.7%
France	9 1.2%
Hungary	14 1.9%
Iceland	5 0.7%
Italy	6 0.8%
Korea, Republic of	22 2.9%
New Zealand	1 0.1%
Poland	36 4.8%
Serbia	21 2.8%
South Africa	1 0.1%
Spain	14 1.9%
Ukraine	14 1.9%

Outcome Measures

1. Primary Outcome

Title	Patients With Any Treatment-emergent Adverse Event
Description	Number of patients who experienced 1 or more Treatment Emergent Adverse Event
Time Frame	Visit 1 (Week 0) up to 30 days after Visit 8 (up to Week 48) or Final Visit

Outcome Measure Data

Analysis Population Description

Analysis was performed on the 747 patients who took at least 1 dose of investigational product (Safety Population).

Arm/Group Title	Memantine
Arm/Group Description	To maintain the blind of the preceding study, patients who participated in MEM-MD-68 began this study with 6 weeks of double blind dosing during which all patients were either titrated to or remained on their maximum target dosages. This was followed by up-to 42 weeks of open-label dosing. Patients who took open-label memantine in the preceding study, MEM-MD-67 or MEM-MD-91, received up to 48 weeks of open-label memantine at their maximum tolerated weight based target dosage.
Measure Participants	747
Number [participants]	424 56.8%

Adverse Events

Time Frame	Adverse Event data was collected from October 2012 to February 2014 at 106 sites in the US and 15 other countries.
Adverse Event Reporting Description	Safety results are based on the safety population (ie, all patients who took at least one dose of investigational product).
Arm/Group Title	Memantine
Arm/Group Description	To maintain the blind of the preceding study, patients who participated in MEM-MD-68 began this study with 6 weeks of double blind dosing during which all patients were either titrated to or remained on their maximum target dosages. This was followed by up-to 42 weeks of open-label dosing. Patients who took open-label memantine in the preceding study, MEM-MD-67 or MEM-MD-91, received up to 48 weeks of open-label memantine at their maximum tolerated weight based target dosage.
All Cause Mortality
	Memantine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Memantine
	Affected / at Risk (%)	# Events
Total	8/747 (1.1%)
Gastrointestinal disorders
Abdominal pain	1/747 (0.1%)
Abdominal pain lower	1/747 (0.1%)
Vomiting	1/747 (0.1%)
Infections and infestations
Appendicitis	1/747 (0.1%)
Injury, poisoning and procedural complications
Foreign body	1/747 (0.1%)
Rectal prolapse	1/747 (0.1%)
Investigations
Dehydration	1/747 (0.1%)
Nervous system disorders
Abnormal behaviour	1/747 (0.1%)
Dysphoria	1/747 (0.1%)
Homicidal ideation	1/747 (0.1%)
Suicidal ideation	1/747 (0.1%)
Other (Not Including Serious) Adverse Events
	Memantine
	Affected / at Risk (%)	# Events
Total	150/747 (20.1%)
Gastrointestinal disorders
Vomiting	51/747 (6.8%)
General disorders
Pyrexia	47/747 (6.3%)
Infections and infestations
Nasopharyngitis	55/747 (7.4%)
Nervous system disorders
Headache	41/747 (5.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

All data generated in this study will be the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the PI will be subject to mutual agreement between the PI and Forest Research Institute, Inc.