40 Week Extension Study Of Asenapine and Olanzapine For Bipolar Disorder (A7501007)(COMPLETED)(P05857)
Study Details
Study Description
Brief Summary
Bipolar disorder is characterized by mood swings that range from from high (manic) to low (depressed) states. Sometimes, symptoms of both depression and mania are present (mixed episodes). Asenapine is an investigational medication for the treatment of manic or mixed episodes of bipolar disorder. Patients who completed study A7501006 (a 9 week extension study) could continue with the same treatment that they had been receiving: asenapine or olanzapine (a medication that is already approved for the treatment of bipolar mania) in a 40 -week continuation study.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Asenapine Asenapine 5-10 mg twice daily for 40 weeks |
Drug: asenapine
Asenapine, 40 weeks
Other Names:
|
Active Comparator: Olanzapine Olanzapine 5-20 mg once daily for 40 weeks |
Drug: Olanzapine
Olanzapine, 40 weeks
|
Outcome Measures
Primary Outcome Measures
- Participants Who Experienced Adverse Event(s) [Up to 40 weeks]
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.
- Number of Participants With Abnormal Physical Examination Findings [Week 40 or endpoint]
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.
- Number of Participants With Abnormal Electrocardiogram [Week 40 or endpoint]
This is the number of participants with electrocardiogram (ECG) adverse events.
- Body Weight [Baseline to Week 40 or endpoint]
Weight change from baseline
- Extrapyramidal Symptoms [EPS] [Week 40 or endpoint]
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.
- Concomitant Medications [Up to 40 weeks]
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.
- Abdominal Girth [Baseline to Week 40 or endpoint]
Change in abdominal girth from baseline
- Number of Participants With Markedly Abnormal Vital Sign Changes [Post-baseline (at Week 4, 12, 20, 28, and 40 or endpoint)]
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.
- Number of Participants With Laboratory Values Outside Normal Range [Week 40 or endpoint]
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
Eligibility Criteria
Criteria
Inclusion Criteria:
- Have completed asenapine 3-week and 9 -week studies for the treatment of an acute manic or mixed episode and not had any major protocol violations..
Exclusion Criteria:
- Patients with unstable medical conditions or clinically significant laboratory
abnormalities.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Organon and Co
- Pfizer
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- P05857
- A7501007
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Placebo/Asenapine | Asenapine | Olanzapine |
---|---|---|---|
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 |
Baseline Characteristics
Arm/Group Title | Placebo/Asenapine | Asenapine | Olanzapine | Total |
---|---|---|---|---|
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 Participants | 32 | 79 | 107 | 218 |
Age (Count of Participants) | ||||
<=18 years |
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 (Count of 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%
|
Outcome Measures
Title | Participants Who Experienced Adverse Event(s) |
---|---|
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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Placebo/Asenapine | Asenapine | Olanzapine |
---|---|---|---|
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 |
Measure Participants | 32 | 79 | 107 |
Number [Participants] |
23
71.9%
|
68
86.1%
|
85
79.4%
|
Title | Number of Participants With Abnormal Physical Examination Findings |
---|---|
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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | All Treatment Groups |
---|---|
Arm/Group Description | Asenapine 5-10 mg twice daily for 40 weeks or Olanzapine 5-20 mg daily for 40 weeks |
Measure Participants | 218 |
Number [Participants] |
32
100%
|
Title | Number of Participants With Abnormal Electrocardiogram |
---|---|
Description | This is the number of participants with electrocardiogram (ECG) adverse events. |
Time Frame | Week 40 or endpoint |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Placebo/Asenapine | Asenapine | Olanzapine |
---|---|---|---|
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 |
Measure Participants | 32 | 79 | 107 |
Sinus bradycardia |
0
0%
|
2
2.5%
|
0
0%
|
Bundle branch block right |
0
0%
|
1
1.3%
|
0
0%
|
ECG QRS complex prolonged |
0
0%
|
0
0%
|
1
0.9%
|
ECG ST segment depression |
0
0%
|
0
0%
|
1
0.9%
|
ECG T wave inversion |
0
0%
|
0
0%
|
1
0.9%
|
Supraventricular extrasystoles |
0
0%
|
0
0%
|
1
0.9%
|
Ventricular extrasystoles |
0
0%
|
0
0%
|
1
0.9%
|
Title | Body Weight |
---|---|
Description | Weight change from baseline |
Time Frame | Baseline to Week 40 or endpoint |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Placebo/Asenapine | Asenapine | Olanzapine |
---|---|---|---|
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 |
Measure Participants | 32 | 79 | 107 |
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)
|
Title | Extrapyramidal Symptoms [EPS] |
---|---|
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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Placebo/Asenapine | Asenapine | Olanzapine |
---|---|---|---|
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 |
Measure Participants | 32 | 79 | 107 |
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)
|
Title | Concomitant Medications |
---|---|
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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Placebo/Asenapine | Asenapine | Olanzapine |
---|---|---|---|
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 |
Measure Participants | 32 | 79 | 107 |
Participants with no concomitant medications |
10
31.3%
|
21
26.6%
|
31
29%
|
Participants with >=1 concomitant medication |
22
68.8%
|
58
73.4%
|
76
71%
|
Title | Abdominal Girth |
---|---|
Description | Change in abdominal girth from baseline |
Time Frame | Baseline to Week 40 or endpoint |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Placebo/Asenapine | Asenapine | Olanzapine |
---|---|---|---|
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 |
Measure Participants | 32 | 79 | 107 |
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)
|
Title | Number of Participants With Markedly Abnormal Vital Sign Changes |
---|---|
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) |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Placebo/Asenapine | Asenapine | Olanzapine |
---|---|---|---|
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 |
Measure Participants | 32 | 79 | 107 |
Number [Participants] |
2
6.3%
|
12
15.2%
|
11
10.3%
|
Title | Number of Participants With Laboratory Values Outside Normal Range |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|---|
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 |
Measure Participants | 32 | 79 | 107 |
Biochemistry |
25
78.1%
|
76
96.2%
|
115
107.5%
|
Metabolic chemistry |
17
53.1%
|
32
40.5%
|
96
89.7%
|
Endocrinology/miscellaneous |
7
21.9%
|
35
44.3%
|
39
36.4%
|
Hematology |
22
68.8%
|
90
113.9%
|
83
77.6%
|
Adverse Events
Time Frame | ||||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||
Arm/Group Title | Placebo/Asenapine | Asenapine | Olanzapine | |||
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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
Placebo/Asenapine | Asenapine | Olanzapine | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/32 (6.3%) | 6/79 (7.6%) | 9/107 (8.4%) | |||
Cardiac disorders | ||||||
Cardiac failure | 0/32 (0%) | 0 | 0/79 (0%) | 0 | 1/107 (0.9%) | 1 |
General disorders | ||||||
Death neonatal | 0/32 (0%) | 0 | 1/79 (1.3%) | 1 | 0/107 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||
Drug exposure during pregnancy | 0/32 (0%) | 0 | 1/79 (1.3%) | 1 | 0/107 (0%) | 0 |
Psychiatric disorders | ||||||
Bipolar I disorder | 0/32 (0%) | 0 | 1/79 (1.3%) | 1 | 2/107 (1.9%) | 2 |
Completed suicide | 0/32 (0%) | 0 | 0/79 (0%) | 0 | 1/107 (0.9%) | 1 |
Depression | 2/32 (6.3%) | 2 | 3/79 (3.8%) | 3 | 3/107 (2.8%) | 3 |
Mania | 0/32 (0%) | 0 | 0/79 (0%) | 0 | 2/107 (1.9%) | 2 |
Psychotic disorder | 0/32 (0%) | 0 | 1/79 (1.3%) | 1 | 0/107 (0%) | 0 |
Suicidal ideation | 1/32 (3.1%) | 1 | 0/79 (0%) | 0 | 0/107 (0%) | 0 |
Suicide attempt | 0/32 (0%) | 0 | 0/79 (0%) | 0 | 1/107 (0.9%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
Placebo/Asenapine | Asenapine | Olanzapine | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 12/32 (37.5%) | 28/79 (35.4%) | 34/107 (31.8%) | |||
Gastrointestinal disorders | ||||||
Dyspepsia | 2/32 (6.3%) | 2 | 1/79 (1.3%) | 1 | 0/107 (0%) | 0 |
General disorders | ||||||
Fatigue | 1/32 (3.1%) | 1 | 1/79 (1.3%) | 1 | 7/107 (6.5%) | 7 |
Pyrexia | 0/32 (0%) | 0 | 2/79 (2.5%) | 3 | 6/107 (5.6%) | 6 |
Infections and infestations | ||||||
Nasopharyngitis | 2/32 (6.3%) | 2 | 1/79 (1.3%) | 1 | 4/107 (3.7%) | 6 |
Investigations | ||||||
Weight decreased | 3/32 (9.4%) | 3 | 4/79 (5.1%) | 4 | 0/107 (0%) | 0 |
Weight increased | 1/32 (3.1%) | 2 | 5/79 (6.3%) | 5 | 8/107 (7.5%) | 8 |
Musculoskeletal and connective tissue disorders | ||||||
Back pain | 2/32 (6.3%) | 2 | 2/79 (2.5%) | 2 | 1/107 (0.9%) | 1 |
Nervous system disorders | ||||||
Parkinsonism | 2/32 (6.3%) | 2 | 2/79 (2.5%) | 2 | 1/107 (0.9%) | 4 |
Sedation | 1/32 (3.1%) | 1 | 5/79 (6.3%) | 5 | 5/107 (4.7%) | 7 |
Somnolence | 2/32 (6.3%) | 2 | 3/79 (3.8%) | 3 | 3/107 (2.8%) | 3 |
Insomnia | 2/32 (6.3%) | 5 | 6/79 (7.6%) | 7 | 7/107 (6.5%) | 14 |
Psychiatric disorders | ||||||
Depression | 2/32 (6.3%) | 2 | 7/79 (8.9%) | 8 | 5/107 (4.7%) | 5 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
Name/Title | Senior Vice President, Global Clinical Development |
---|---|
Organization | Merck Sharp & Dohme Corp. |
Phone | |
ClinicalTrialsDisclosure@merck.com |
- P05857
- A7501007