Trial Outcomes & Findings for A Study Of Sertraline Compared With Paroxetine In The Treatment Of Panic Disorder (NCT NCT00677352)

Last Updated: 2021-01-27

Results Overview

Panic and Agoraphobia Scale has 13 items with a 5-point scale (range: 0 to 4). The total possible score is ranged from 0 to 52. The increasing value are considered worse outcome. The scale is grouped into 5 subscores (not including item U in total score): panic attacks ; agoraphobia/avoidance behavior ; anticipatory anxiety; disability; and health worries. Four point difference in reduction of the PAS total score has been identified as not clinically meaningful in the assessment of Panic Disorder symptomatology.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

321 participants

Primary outcome timeframe

Baseline and 12 weeks

Results posted on

2021-01-27

Participant Flow

Participants were screened at 34 centers in Japan.

Subjects who experienced at least one panic attack that met the DSM-IV diagnostic criteria per week between the start of the washout/observation period and the start of the double-blind treatment period and who had a total score of 18 or higher on the Panic and Agoraphobia Scale at the start of the double-blind treatment period.

Participant milestones

Participant milestones
Measure	Sertraline Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks.	Paroxetine Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
Treatment Phase STARTED	157	164
Treatment Phase COMPLETED	132	122
Treatment Phase NOT COMPLETED	25	42
Tapering Phase STARTED	132	122
Tapering Phase COMPLETED	126	112
Tapering Phase NOT COMPLETED	6	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Sertraline Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks.	Paroxetine Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
Treatment Phase Adverse Event	14	22
Treatment Phase Lack of Efficacy	2	3
Treatment Phase Lost to Follow-up	0	1
Treatment Phase Withdrawal by Subject	7	7
Treatment Phase Physician Decision	1	0
Treatment Phase Pregnancy	0	1
Treatment Phase Protocol Violation	1	1
Treatment Phase Transference or work related matter	0	5
Treatment Phase Not treated	0	2
Tapering Phase Adverse Event	1	5
Tapering Phase Withdrawal by Subject	5	3
Tapering Phase Pregnancy	0	1
Tapering Phase Job transfer	0	1

Baseline Characteristics

A Study Of Sertraline Compared With Paroxetine In The Treatment Of Panic Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sertraline n=157 Participants Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks.	Paroxetine n=162 Participants Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.	Total n=319 Participants Total of all reporting groups
Age, Customized < 18 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Age, Customized 18 - 44 years	119 participants n=5 Participants	126 participants n=7 Participants	245 participants n=5 Participants
Age, Customized 45 -64 years	38 participants n=5 Participants	36 participants n=7 Participants	74 participants n=5 Participants
Age, Customized >= 65 years	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Sex: Female, Male Female	113 Participants n=5 Participants	109 Participants n=7 Participants	222 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	53 Participants n=7 Participants	97 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: Efficacy Evaluable Set: A subset of patients in the Full Analysis Set who met some inclusion (diagnosis of Panic Disorder, etc.) and exclusion (psychotherapy, etc.) criteria, had to be treated for a minimum of 8 weeks and had a PAS score at least one evaluation during Week 8 to 12. Last Observation Carried Forward

Outcome measures

Outcome measures
Measure	Sertraline n=127 Participants Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks.	Paroxetine n=127 Participants Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
Mean Change From Baseline in Panic and Agoraphobia Scale (PAS) Total Score at the End of Treatment Phase	-17.4 Scores on scale Interval -18.9 to -15.9	-17.0 Scores on scale Interval -18.4 to -15.5

SECONDARY outcome

Timeframe: 12 weeks

The ratings were rated to compare with baseline by 7-point " 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse". Responder was defined as number of participants who were assessed as "very much improved" or " much improved".

Outcome measures

Outcome measures
Measure	Sertraline n=127 Participants Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks.	Paroxetine n=127 Participants Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
Percentage of Participants of Responder in Clinical Global Impression (CGI) - Improvement	83.5 Percentage of participants	85.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Panic attacks were defined as having four or more of the following Diagnostic and Statistical Manual of Mental Disorders symptoms. Palpitations or increased heart rate, Sweating, Trembling or shaking, Shortness of breath or smothering sensations, Choking, Chest pain or discomfort, Nausea or upset stomach, Dizziness, unsteady feelings or faintness, Feeling unlike yourself, or detached from a situation and/or like things happening around you are strange and unreal, Fear of going crazy or doing something uncontrolled, Fear of dying, Abnormal sense, Hot flashes or chills.

Outcome measures

Outcome measures
Measure	Sertraline n=127 Participants Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks.	Paroxetine n=127 Participants Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
Mean Change From Baseline in Panic Attack at the End of Treatment Phase	-4.07 panic attacks per week Standard Deviation 6.12	-4.59 panic attacks per week Standard Deviation 7.52

SECONDARY outcome

Timeframe: Baseline and 12 weeks

The Hamilton Anxiety Rating Scale provided a 5-point intensity rating (0=None to 4=Very severe) of anxiety symptoms in 14 items. The increasing values are considered worse outcome. The total possible score is ranged from 0 to 52.

Outcome measures

Outcome measures
Measure	Sertraline n=127 Participants Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks.	Paroxetine n=127 Participants Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
Mean Change From Baseline in Hamilton Anxiety Rating Scale Total Score at the End of Treatment Phase	-11.35 Scores on a scale Standard Deviation 10.45	-10.36 Scores on a scale Standard Deviation 8.27

SECONDARY outcome

Timeframe: 1, 2, 4, 6, 8 10 and 12 weeks (or study discontinuation) after administration of study drug

Population: The safety analysis set : Subset of patients who had taken at least one dose of the study drug and who had visited the study center at least once after taking the study drug.

Number of sparticipants with all causality adverse events, serious adverse events, severe adverse events, adverse events resulted in discontinuation, dose reduced or temporary discontinuation. Participants were counted only once per treatment in each row.

Outcome measures

Outcome measures
Measure	Sertraline n=157 Participants Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks.	Paroxetine n=162 Participants Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
Number of Participants With Summary of Adverse Events in Treatment Phase Subjects with adverse events	127 Participants	134 Participants
Number of Participants With Summary of Adverse Events in Treatment Phase Subjects with serious adverse events	1 Participants	1 Participants
Number of Participants With Summary of Adverse Events in Treatment Phase Subjects with severe adverse events	3 Participants	14 Participants
Number of Participants With Summary of Adverse Events in Treatment Phase Subjects discontinued due to adverse events	14 Participants	23 Participants
Number of Participants With Summary of Adverse Events in Treatment Phase Dose reduced or temporary discontinuation	13 Participants	14 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: The safety analysis set : Subset of patients who had taken at least one dose of the study drug and who had visited the study center at least once after taking the study drug.

Number of subjects with all causality adverse events, serious adverse events, severe adverse events, adverse events resulted in discontinuation, dose reduced or temporary discontinuation. Subjects were counted only once per treatment in each row.

Outcome measures

Outcome measures
Measure	Sertraline n=132 Participants Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks.	Paroxetine n=122 Participants Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
Summary of Adverse Events in Tapering Phase Subjects with adverse events	73 Participants	87 Participants
Summary of Adverse Events in Tapering Phase Subjects with serious adverse events	1 Participants	0 Participants
Summary of Adverse Events in Tapering Phase Subjects with severe adverse events	11 Participants	16 Participants
Summary of Adverse Events in Tapering Phase Subjects discontinued due to adverse events	1 Participants	4 Participants
Summary of Adverse Events in Tapering Phase Dose reduced or temporary discontinuation	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 4 weeks

Population: Completer Set : Subset of patients in the EES who had a PAS rating at Week 16.

The percentage of participants divided was calcurated as follows: Devide the number of participants who had experienced new symptoms in Week 16, regardless of causal relationship with the study drug, or worsening of the severity in Week 16 compared with Week 12, by total number of participants in each treatment group.

Outcome measures

Outcome measures
Measure	Sertraline n=124 Participants Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks.	Paroxetine n=118 Participants Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
Percentage of Participants With Deterioration in Antidepressant Discontinuation Scale During Tapering Phase	59.7 Percentage of participants	76.3 Percentage of participants

Adverse Events

Sertraline

Serious events: 2 serious events

Other events: 132 other events

Deaths: 0 deaths

Paroxetine

Serious events: 1 serious events

Other events: 137 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sertraline n=157 participants at risk Treatment phase was started from 25 mg/day followed by increase to 50 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 75 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 100 mg/day. At tapering phase, 50 mg/day was administered for 1 week after Week 12, followed by 25 mg/day for 1 week, and no study medication during the last 2 weeks.	Paroxetine n=162 participants at risk Treatment phase was started from 10 mg/day followed by increase to 20 mg/day at Week 1, and treatment was continued for 3 weeks. If there was no tolerability concern at Week 4 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day and treatment was continued for 2 weeks. If there was no tolerability concern at Week 6 at the discretion of the investigator (or subinvestigator), the dose was increased to 30 mg/day. At tapering phase, 20 mg/day was administered for 1 week after Week 12, followed by 10 mg/day for 1 week, and no study medication during the last 2 weeks.
Infections and infestations Enteritis infectious	0.00% 0/157 • 16 weeks The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.62% 1/162 • 16 weeks The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Suicidal ideation	0.64% 1/157 • 16 weeks The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/162 • 16 weeks The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Erythema multiforme	0.64% 1/157 • 16 weeks The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/162 • 16 weeks The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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