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Trial record 4 of 69 for:    "Bipolar Disorder" | "Olanzapine"

40 Week Extension Study Of Asenapine and Olanzapine For Bipolar Disorder (A7501007)(COMPLETED)(P05857)

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ClinicalTrials.gov Identifier: NCT00159783
Recruitment Status : Completed
First Posted : September 12, 2005
Results First Posted : July 16, 2010
Last Update Posted : February 25, 2015
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Bipolar Disorder
Interventions Drug: asenapine
Drug: Olanzapine
Enrollment 218
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
Hide Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks
Period Title: Overall Study
Started 32 79 107
Completed 13 52 68
Not Completed 19 27 39
Reason Not Completed
Adverse Event             5             7             9
Lack of Efficacy             1             2             3
Withdrawal by Subject             7             11             12
Lost to Follow-up             6             5             11
not specified             0             2             4
Arm/Group Title Placebo/Asenapine Asenapine Olanzapine Total
Hide Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks Total of all reporting groups
Overall Number of Baseline Participants 32 79 107 218
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 79 participants 107 participants 218 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
31
  96.9%
77
  97.5%
106
  99.1%
214
  98.2%
>=65 years
1
   3.1%
2
   2.5%
1
   0.9%
4
   1.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 79 participants 107 participants 218 participants
Female
15
  46.9%
43
  54.4%
39
  36.4%
97
  44.5%
Male
17
  53.1%
36
  45.6%
68
  63.6%
121
  55.5%
1.Primary Outcome
Title Participants Who Experienced Adverse Event(s)
Hide Description

Adverse event (AE) data, both serious and non-serious, were collected. Serious AEs were also collected up to 30 days post last dose of study drug.

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product. It does not necessarily have to have a causal relationship with this treatment.

An AE is defined as serious if it results in death, is life-threatening, requires in-patient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

Time Frame Up to 40 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
Hide Arm/Group Description:
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)
Olanzapine 5-20 mg once daily for 40 weeks
Overall Number of Participants Analyzed 32 79 107
Measure Type: Number
Unit of Measure: Participants
23 68 85
2.Primary Outcome
Title Number of Participants With Abnormal Physical Examination Findings
Hide Description Physical exam (PE) included assessment of general appearance, skin, head, eyes, ears, nose, throat, lungs, blood pressure, cardiac rhythm & rate, neurologic status, and abdomen. The findings were deemed to be normal/abnormal based on the clinical judgment of the investigator.
Time Frame Week 40 or endpoint
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Treatment Groups
Hide Arm/Group Description:
Asenapine 5-10 mg twice daily for 40 weeks or Olanzapine 5-20 mg daily for 40 weeks
Overall Number of Participants Analyzed 218
Measure Type: Number
Unit of Measure: Participants
32
3.Primary Outcome
Title Number of Participants With Abnormal Electrocardiogram
Hide Description This is the number of participants with electrocardiogram (ECG) adverse events.
Time Frame Week 40 or endpoint
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
Hide Arm/Group Description:
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)
Olanzapine 5-20 mg once daily for 40 weeks
Overall Number of Participants Analyzed 32 79 107
Measure Type: Number
Unit of Measure: Participants
Sinus bradycardia 0 2 0
Bundle branch block right 0 1 0
ECG QRS complex prolonged 0 0 1
ECG ST segment depression 0 0 1
ECG T wave inversion 0 0 1
Supraventricular extrasystoles 0 0 1
Ventricular extrasystoles 0 0 1
4.Primary Outcome
Title Body Weight
Hide Description Weight change from baseline
Time Frame Baseline to Week 40 or endpoint
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
Hide Arm/Group Description:
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)
Olanzapine 5-20 mg once daily for 40 weeks
Overall Number of Participants Analyzed 32 79 107
Mean (Standard Deviation)
Unit of Measure: Kilograms
Baseline 81.4  (19.94) 68.1  (17.22) 72.0  (19.96)
Change from baseline to Week 40 or endpoint 1.7  (5.95) 3.5  (6.65) 6.0  (6.59)
5.Primary Outcome
Title Extrapyramidal Symptoms [EPS]
Hide Description

EPS was assessed using the (1) involuntary movement scale [AIMS], (2) Barnes Akathisia Rating Scale [BARS], and (3) Simpson Angus Rating Scale SARS.

AIMS score range 0-4; higher scores indicate greater symptom severity.

BARS score rang 0-9; higher scores indicate greater severity of akathisia.

SARS score range 0-40; higher scores indicate greater degree of Parkinsonism.

Time Frame Week 40 or endpoint
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
Hide Arm/Group Description:
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)
Olanzapine 5-20 mg once daily for 40 weeks
Overall Number of Participants Analyzed 32 79 107
Mean (Standard Deviation)
Unit of Measure: Units on a scale
AIMS 0.4  (1.37) 0.1  (0.60) 0.0  (0.14)
BARS 0.4  (1.21) 0.2  (0.77) 0.1  (0.55)
SARS 0.6  (1.72) 0.2  (1.36) 0.3  (1.15)
6.Primary Outcome
Title Concomitant Medications
Hide Description

Concomitant medications are any medications taken on or after the date of first dose of double-blind study drug through the date of

last dose of double-blind study drug.

Time Frame Up to 40 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
Hide Arm/Group Description:
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)
Olanzapine 5-20 mg once daily for 40 weeks
Overall Number of Participants Analyzed 32 79 107
Measure Type: Number
Unit of Measure: Participants
Participants with no concomitant medications 10 21 31
Participants with >=1 concomitant medication 22 58 76
7.Primary Outcome
Title Abdominal Girth
Hide Description Change in abdominal girth from baseline
Time Frame Baseline to Week 40 or endpoint
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
Hide Arm/Group Description:
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)
Olanzapine 5-20 mg once daily for 40 weeks
Overall Number of Participants Analyzed 32 79 107
Mean (Standard Deviation)
Unit of Measure: Centimeters (cm)
Baseline 91.1  (14.20) 86.8  (14.79) 89.4  (14.78)
Change from baseline to Week 40 or endpoint 3.0  (6.84) 2.6  (6.87) 5.0  (7.89)
8.Primary Outcome
Title Number of Participants With Markedly Abnormal Vital Sign Changes
Hide Description

Vital signs measured: sitting blood pressure, heart rate.

Definitions:

Markedly abnormal decreases: heart rate (HR) – if ≤50 bpm and decrease from baseline of ≥15 beats per minute (bpm); systolic blood pressure (SBP) – if ≤90 mm Hg and decrease from baseline of ≥20 mm Hg; diastolic blood pressure (DBP) – if ≤50 mm Hg and decrease from baseline of ≥15 mm Hg.

Markedly abnormal increases: HR – if ≥110 bpm and increase from baseline of ≥15 bpm; SBP – if ≥180 mm Hg and increase from baseline of ≥20 mm Hg; DBP – if ≥105 mm Hg and increase from baseline of ≥15 mm Hg.

Time Frame Post-baseline (at Week 4, 12, 20, 28, and 40 or endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
Hide Arm/Group Description:
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)
Olanzapine 5-20 mg once daily for 40 weeks
Overall Number of Participants Analyzed 32 79 107
Measure Type: Number
Unit of Measure: Participants
2 12 11
9.Primary Outcome
Title Number of Participants With Laboratory Values Outside Normal Range
Hide Description

Normal ranges were provided by the central laboratory.

Biochemistry = electrolytes, creatine kinase, liver enzymes, blood urea nitrogen, creatinine, alkaline phosphatase, protein, albumin

Metabolic chemistry = cholesterol, glucose, triglycerides, glycosylated hemoglobin

Endocrinology/miscellaneous = insulin, prolactin

Hematology = hemoglobin, red blood cell count, white blood cell count, platelets, hematocrit, neutrophils, lymphocytes, monocytes, eosinophils, basophils

Time Frame Week 40 or endpoint
Hide Outcome Measure Data
Hide Analysis Population Description

Number at risk = participants with either normal or abnormal baseline value and a non-missing value at endpoint.

Actual at risk: 20-32 for placebo/asenapine arm; 50-78 for asenapine arm; 63-106 in olanzapine arm.

Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
Hide Arm/Group Description:
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)
Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)
Olanzapine 5-20 mg once daily for 40 weeks
Overall Number of Participants Analyzed 32 79 107
Measure Type: Number
Unit of Measure: Participants
Biochemistry 25 76 115
Metabolic chemistry 17 32 96
Endocrinology/miscellaneous 7 35 39
Hematology 22 90 83
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo/Asenapine Asenapine Olanzapine
Hide Arm/Group Description Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study) Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study) Olanzapine 5-20 mg once daily for 40 weeks
All-Cause Mortality
Placebo/Asenapine Asenapine Olanzapine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo/Asenapine Asenapine Olanzapine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/32 (6.25%)      6/79 (7.59%)      9/107 (8.41%)    
Cardiac disorders       
Cardiac failure  1  0/32 (0.00%)  0 0/79 (0.00%)  0 1/107 (0.93%)  1
General disorders       
Death neonatal  2  0/32 (0.00%)  0 1/79 (1.27%)  1 0/107 (0.00%)  0
Injury, poisoning and procedural complications       
Drug exposure during pregnancy  2  0/32 (0.00%)  0 1/79 (1.27%)  1 0/107 (0.00%)  0
Psychiatric disorders       
Bipolar I disorder  2  0/32 (0.00%)  0 1/79 (1.27%)  1 2/107 (1.87%)  2
Completed suicide  1  0/32 (0.00%)  0 0/79 (0.00%)  0 1/107 (0.93%)  1
Depression  1  2/32 (6.25%)  2 3/79 (3.80%)  3 3/107 (2.80%)  3
Mania  1  0/32 (0.00%)  0 0/79 (0.00%)  0 2/107 (1.87%)  2
Psychotic disorder  1  0/32 (0.00%)  0 1/79 (1.27%)  1 0/107 (0.00%)  0
Suicidal ideation  1  1/32 (3.13%)  1 0/79 (0.00%)  0 0/107 (0.00%)  0
Suicide attempt  1  0/32 (0.00%)  0 0/79 (0.00%)  0 1/107 (0.93%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.1
2
Term from vocabulary, MedDRA (9.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo/Asenapine Asenapine Olanzapine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/32 (37.50%)      28/79 (35.44%)      34/107 (31.78%)    
Gastrointestinal disorders       
Dyspepsia  1  2/32 (6.25%)  2 1/79 (1.27%)  1 0/107 (0.00%)  0
General disorders       
Fatigue  1  1/32 (3.13%)  1 1/79 (1.27%)  1 7/107 (6.54%)  7
Pyrexia  1  0/32 (0.00%)  0 2/79 (2.53%)  3 6/107 (5.61%)  6
Infections and infestations       
Nasopharyngitis  1  2/32 (6.25%)  2 1/79 (1.27%)  1 4/107 (3.74%)  6
Investigations       
Weight decreased  1  3/32 (9.38%)  3 4/79 (5.06%)  4 0/107 (0.00%)  0
Weight increased  1  1/32 (3.13%)  2 5/79 (6.33%)  5 8/107 (7.48%)  8
Musculoskeletal and connective tissue disorders       
Back pain  1  2/32 (6.25%)  2 2/79 (2.53%)  2 1/107 (0.93%)  1
Nervous system disorders       
Parkinsonism  1  2/32 (6.25%)  2 2/79 (2.53%)  2 1/107 (0.93%)  4
Sedation  1  1/32 (3.13%)  1 5/79 (6.33%)  5 5/107 (4.67%)  7
Somnolence  1  2/32 (6.25%)  2 3/79 (3.80%)  3 3/107 (2.80%)  3
Insomnia  1  2/32 (6.25%)  5 6/79 (7.59%)  7 7/107 (6.54%)  14
Psychiatric disorders       
Depression  1  2/32 (6.25%)  2 7/79 (8.86%)  8 5/107 (4.67%)  5
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

If study is part of a multicenter trial, Investigator agrees that the first publication is to be a joint publication covering all centers. However, if a joint manuscript has not been submitted for publication within 12 mos of completion or termination of study at all participating sites, Investigator is free to publish separately.

The sponsor should review any publication prior to submission for publication to ensure no confidential information is released inadvertently.

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00159783     History of Changes
Other Study ID Numbers: P05857
A7501007
First Submitted: September 8, 2005
First Posted: September 12, 2005
Results First Submitted: April 15, 2010
Results First Posted: July 16, 2010
Last Update Posted: February 25, 2015