Trial Outcomes & Findings for 40 Week Extension Study Of Asenapine and Olanzapine For Bipolar Disorder (A7501007)(COMPLETED)(P05857) (NCT NCT00159783)

NCT ID: NCT00159783

Last Updated: 2022-02-09

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 218 participants
• Primary outcome timeframe: Up to 40 weeks
• Results posted on: 2022-02-09

Participant Flow

Participant milestones

Measure	Placebo/Asenapine Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine Olanzapine 5-20 mg once daily for 40 weeks
Overall Study STARTED	32	79	107
Overall Study COMPLETED	13	52	68
Overall Study NOT COMPLETED	19	27	39

Reasons for withdrawal

Measure	Placebo/Asenapine Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine Olanzapine 5-20 mg once daily for 40 weeks
Overall Study Adverse Event	5	7	9
Overall Study Lack of Efficacy	1	2	3
Overall Study Withdrawal by Subject	7	11	12
Overall Study Lost to Follow-up	6	5	11
Overall Study Other	0	2	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo/Asenapine n=32 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine n=79 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine n=107 Participants Olanzapine 5-20 mg once daily for 40 weeks	Total n=218 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	31 Participants n=5 Participants	77 Participants n=7 Participants	106 Participants n=5 Participants	214 Participants n=4 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	43 Participants n=7 Participants	39 Participants n=5 Participants	97 Participants n=4 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	36 Participants n=7 Participants	68 Participants n=5 Participants	121 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo/Asenapine n=32 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine n=79 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine n=107 Participants Olanzapine 5-20 mg once daily for 40 weeks
Participants Who Experienced Adverse Event(s)	23 Participants	68 Participants	85 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo/Asenapine n=218 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine Olanzapine 5-20 mg once daily for 40 weeks
Number of Participants With Abnormal Physical Examination Findings	32 Participants	—	—

PRIMARY outcome

Timeframe: Week 40 or endpoint

This is the number of participants with electrocardiogram (ECG) adverse events.

Outcome measures

Measure	Placebo/Asenapine n=32 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine n=79 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine n=107 Participants Olanzapine 5-20 mg once daily for 40 weeks
Number of Participants With Abnormal Electrocardiogram Sinus bradycardia	0 Participants	2 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram Bundle branch block right	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram ECG QRS complex prolonged	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Electrocardiogram ECG ST segment depression	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Electrocardiogram ECG T wave inversion	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Electrocardiogram Supraventricular extrasystoles	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Electrocardiogram Ventricular extrasystoles	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline to Week 40 or endpoint

Weight change from baseline

Outcome measures

Measure	Placebo/Asenapine n=32 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine n=79 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine n=107 Participants Olanzapine 5-20 mg once daily for 40 weeks
Body Weight Baseline	81.4 Kilograms Standard Deviation 19.94	68.1 Kilograms Standard Deviation 17.22	72.0 Kilograms Standard Deviation 19.96
Body Weight Change from baseline to Week 40 or endpoint	1.7 Kilograms Standard Deviation 5.95	3.5 Kilograms Standard Deviation 6.65	6.0 Kilograms Standard Deviation 6.59

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo/Asenapine n=32 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine n=79 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine n=107 Participants Olanzapine 5-20 mg once daily for 40 weeks
Extrapyramidal Symptoms [EPS] AIMS	0.4 Units on a scale Standard Deviation 1.37	0.1 Units on a scale Standard Deviation 0.60	0.0 Units on a scale Standard Deviation 0.14
Extrapyramidal Symptoms [EPS] BARS	0.4 Units on a scale Standard Deviation 1.21	0.2 Units on a scale Standard Deviation 0.77	0.1 Units on a scale Standard Deviation 0.55
Extrapyramidal Symptoms [EPS] SARS	0.6 Units on a scale Standard Deviation 1.72	0.2 Units on a scale Standard Deviation 1.36	0.3 Units on a scale Standard Deviation 1.15

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo/Asenapine n=32 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine n=79 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine n=107 Participants Olanzapine 5-20 mg once daily for 40 weeks
Concomitant Medications Participants with no concomitant medications	10 Participants	21 Participants	31 Participants
Concomitant Medications Participants with >=1 concomitant medication	22 Participants	58 Participants	76 Participants

PRIMARY outcome

Timeframe: Baseline to Week 40 or endpoint

Change in abdominal girth from baseline

Outcome measures

Measure	Placebo/Asenapine n=32 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine n=79 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine n=107 Participants Olanzapine 5-20 mg once daily for 40 weeks
Abdominal Girth Baseline	91.1 Centimeters (cm) Standard Deviation 14.20	86.8 Centimeters (cm) Standard Deviation 14.79	89.4 Centimeters (cm) Standard Deviation 14.78
Abdominal Girth Change from baseline to Week 40 or endpoint	3.0 Centimeters (cm) Standard Deviation 6.84	2.6 Centimeters (cm) Standard Deviation 6.87	5.0 Centimeters (cm) Standard Deviation 7.89

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo/Asenapine n=32 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine n=79 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine n=107 Participants Olanzapine 5-20 mg once daily for 40 weeks
Number of Participants With Markedly Abnormal Vital Sign Changes	2 Participants	12 Participants	11 Participants

PRIMARY outcome

Timeframe: Week 40 or endpoint

Population: 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.

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

Outcome measures

Measure	Placebo/Asenapine n=32 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine n=79 Participants Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine n=107 Participants Olanzapine 5-20 mg once daily for 40 weeks
Number of Participants With Laboratory Values Outside Normal Range Biochemistry	25 Participants	76 Participants	115 Participants
Number of Participants With Laboratory Values Outside Normal Range Metabolic chemistry	17 Participants	32 Participants	96 Participants
Number of Participants With Laboratory Values Outside Normal Range Endocrinology/miscellaneous	7 Participants	35 Participants	39 Participants
Number of Participants With Laboratory Values Outside Normal Range Hematology	22 Participants	90 Participants	83 Participants

Adverse Events

Placebo/Asenapine

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Asenapine

Serious events: 6 serious events

Other events: 28 other events

Deaths: 0 deaths

Olanzapine

Serious events: 9 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo/Asenapine n=32 participants at risk Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine n=79 participants at risk Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine n=107 participants at risk Olanzapine 5-20 mg once daily for 40 weeks
Cardiac disorders Cardiac failure	0.00% 0/32	0.00% 0/79	0.93% 1/107 • Number of events 1
General disorders Death neonatal	0.00% 0/32	1.3% 1/79 • Number of events 1	0.00% 0/107
Injury, poisoning and procedural complications Drug exposure during pregnancy	0.00% 0/32	1.3% 1/79 • Number of events 1	0.00% 0/107
Psychiatric disorders Bipolar I disorder	0.00% 0/32	1.3% 1/79 • Number of events 1	1.9% 2/107 • Number of events 2
Psychiatric disorders Completed suicide	0.00% 0/32	0.00% 0/79	0.93% 1/107 • Number of events 1
Psychiatric disorders Depression	6.2% 2/32 • Number of events 2	3.8% 3/79 • Number of events 3	2.8% 3/107 • Number of events 3
Psychiatric disorders Mania	0.00% 0/32	0.00% 0/79	1.9% 2/107 • Number of events 2
Psychiatric disorders Psychotic disorder	0.00% 0/32	1.3% 1/79 • Number of events 1	0.00% 0/107
Psychiatric disorders Suicidal ideation	3.1% 1/32 • Number of events 1	0.00% 0/79	0.00% 0/107
Psychiatric disorders Suicide attempt	0.00% 0/32	0.00% 0/79	0.93% 1/107 • Number of events 1

Other adverse events

Measure	Placebo/Asenapine n=32 participants at risk Asenapine 5-10 mg twice daily for 40 weeks (participants who were on placebo during the 3 week core study)	Asenapine n=79 participants at risk Asenapine 5-10 mg twice daily for 40 weeks (participants who were on asenapine in the 3 week core study)	Olanzapine n=107 participants at risk Olanzapine 5-20 mg once daily for 40 weeks
Gastrointestinal disorders Dyspepsia	6.2% 2/32 • Number of events 2	1.3% 1/79 • Number of events 1	0.00% 0/107
General disorders Fatigue	3.1% 1/32 • Number of events 1	1.3% 1/79 • Number of events 1	6.5% 7/107 • Number of events 7
General disorders Pyrexia	0.00% 0/32	2.5% 2/79 • Number of events 3	5.6% 6/107 • Number of events 6
Infections and infestations Nasopharyngitis	6.2% 2/32 • Number of events 2	1.3% 1/79 • Number of events 1	3.7% 4/107 • Number of events 6
Investigations Weight decreased	9.4% 3/32 • Number of events 3	5.1% 4/79 • Number of events 4	0.00% 0/107
Investigations Weight increased	3.1% 1/32 • Number of events 2	6.3% 5/79 • Number of events 5	7.5% 8/107 • Number of events 8
Musculoskeletal and connective tissue disorders Back pain	6.2% 2/32 • Number of events 2	2.5% 2/79 • Number of events 2	0.93% 1/107 • Number of events 1
Nervous system disorders Parkinsonism	6.2% 2/32 • Number of events 2	2.5% 2/79 • Number of events 2	0.93% 1/107 • Number of events 4
Nervous system disorders Sedation	3.1% 1/32 • Number of events 1	6.3% 5/79 • Number of events 5	4.7% 5/107 • Number of events 7
Nervous system disorders Somnolence	6.2% 2/32 • Number of events 2	3.8% 3/79 • Number of events 3	2.8% 3/107 • Number of events 3
Psychiatric disorders Depression	6.2% 2/32 • Number of events 2	8.9% 7/79 • Number of events 8	4.7% 5/107 • Number of events 5
Nervous system disorders Insomnia	6.2% 2/32 • Number of events 5	7.6% 6/79 • Number of events 7	6.5% 7/107 • Number of events 14

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER