Drug Use Investigation Of Effexor (SECONDARY DATA COLLECTION STUDY; SAFETY AND EFFICACY OF EFFEXOR.UNDER JAPANESE MEDICAL PRACTICE)

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02958527
• Collaborator: (none)
• Enrollment: 1,408
• Actual Duration (Months): 43.2

Study Details

Study Description

Brief Summary

SECONDARY DATA COLLECTION STUDY; SAFETY AND EFFICACY OF EFFEXOR.UNDER JAPANESE MEDICAL PRACTICE

Condition or Disease	Intervention/Treatment	Phase
Depression/Depressed State	Drug: venlafaxine

Detailed Description

This study will be conducted under the central registration system until the number of subjects who meet the conditions for registration reaches the target number of subjects. 12 weeks from the start date. The patients who completed the 12-week treatment with this product will be observed up until Week 52.

Study Design

• Study Type: Observational
• Actual Enrollment: 1408 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: DRUG USE INVESTIGATION OF EFFEXOR(REGISTERED) SR CAPSULES
• Actual Study Start Date: Oct 3, 2016
• Actual Primary Completion Date: May 11, 2020
• Actual Study Completion Date: May 11, 2020

Arms and Interventions

Arm	Intervention/Treatment
venlafaxine Patients with no experience of using time Effexor(venlafaxine) who will be administered time Effexor(venlafaxine)for the first	Drug: venlafaxine; The usual adult starting dosage for oral use is 37.5 mg of venlafaxine once daily, which is increased to 75 mg once daily after a meal from 1 week later. The dose may be adjusted within a range not exceeding 225 mg/day according to the patient's age and symptoms. However, the dose should be increased by 75 mg/day at intervals of not less than 1 week.; Other Names: Effexor

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Drug Reactions [12 weeks from the start date (up until 52 weeks)]

   An adverse drug reaction (ADR) was any untoward medical occurrence attributed to Effexor in a participant who received Effexor. A serious ADR was a ADR resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Relatedness to Effexor was assessed by the physician.

Secondary Outcome Measures

1. Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) Total Scores at Pre-specified Evaluation Points [12 weeks from the start date ( up until 52 weeks)]

   HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with depression (symptoms such as depressed mood, work and activities, sleep, suicide, psychomotor agitation/retardation, appetite, sexual interest, anxiety, and somatic symptoms). The items of the HAM-D17 are rated on a scale of 0 to 2 (8 items) or from 0 to 4 (9 items), and the total score ranges from 0 to 52, higher scores indicating more severity. Change from baseline: mean score at observation minus mean score at baseline. Evaluation was performed at Week 4, 8, 12, 16, 24, 36, and 52.

2. Change From Baseline in the Montgomery - Asberg Depression Rating Scale (MADRS) Total Scores at Pre-specified Evaluation Points [12 weeks from the start date ( up until 52 weeks)]

   MADRS is a clinician-administered rating scale that assesses the overall severity of depressive symptoms. The MADRS had a 10-item checklist (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are scored from 0 to 6, and the total score ranges from 0 to 60, higher scores indicating more severity. Change from baseline: mean score at observation minus mean score at baseline. Evaluation was performed at Week 4, 8, 12, 16, 24, 36, and 52.

3. Clinical Global Impressions-Severity [12 weeks from the start date (up until 52 weeks)]

   CGI-S is a 7-point clinician-administered rating scale that assesses overall severity of the current illness state. The score ranges from 1 to 7, higher scores indicating more affected: "1: normal, not at all ill," "2: borderline mentally ill," "3: mildly ill," "4: moderately ill," "5: markedly ill," "6: severely ill," or "7: among the most extremely ill patients." Evaluation was performed at Week 4, 8, 12, 16, 24, 36, and 52.

4. Changes in the Clinical Global Impressions-Improvement [12 weeks from the start date (up until 52 weeks)]

   CGI-I is a 7-point clinician-administered rating scale that assesses overall improvement of the disease/condition. The score ranges from 1 to 7, higher scores indicating more affected: was assessed as "1: markedly improved," "2: moderately improved," "3: mildly improved," "4: no change," "5: slightly worsened," "6: worsened," or "7: severely worsened." Evaluation was performed at Week 4, 8, 12, 16, 24, 36, and 52.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with no experience of using this product who will be administered this product for the first time

Exclusion Criteria:

• Exclusion criteria are not provided in this study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Study Protocol - Dec 1, 2018
• Statistical Analysis Plan - May 11, 2020

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• ClinicalTrials.gov Identifier: NCT02958527
• Other Study ID Numbers: B2411278
• First Posted: Nov 8, 2016
• Last Update Posted: Jun 16, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Pfizer's Upjohn has merged with Mylan to form Viatris Inc.: Effexor; Depression; Depressed state
• Additional relevant MeSH terms: Depression; Venlafaxine Hydrochloride

Study Results

Participant Flow

Arm/Group Title	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride)
Arm/Group Description	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.
Period Title: Overall Study
STARTED	1408
COMPLETED	1396
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride)
Arm/Group Description	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.
Overall Participants	1334
Age, Customized (Number) [Number]
<15 years	1 0.1%
≥15 and <65 years	1144 85.8%
≥65 years	189 14.2%
Sex: Female, Male (Count of Participants)
Female	687 51.5%
Male	647 48.5%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Drug Reactions
Description	An adverse drug reaction (ADR) was any untoward medical occurrence attributed to Effexor in a participant who received Effexor. A serious ADR was a ADR resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Relatedness to Effexor was assessed by the physician.
Time Frame	12 weeks from the start date (up until 52 weeks)

Outcome Measure Data

Analysis Population Description

The safety analysis set comprised of participants who satisfied the inclusion criteria and had received Effexor at least once.

Arm/Group Title	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride)
Arm/Group Description	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.
Measure Participants	1334
ADR	312 23.4%
Serious ADR	4 0.3%

2. Secondary Outcome

Title	Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) Total Scores at Pre-specified Evaluation Points
Description	HAM-D17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with depression (symptoms such as depressed mood, work and activities, sleep, suicide, psychomotor agitation/retardation, appetite, sexual interest, anxiety, and somatic symptoms). The items of the HAM-D17 are rated on a scale of 0 to 2 (8 items) or from 0 to 4 (9 items), and the total score ranges from 0 to 52, higher scores indicating more severity. Change from baseline: mean score at observation minus mean score at baseline. Evaluation was performed at Week 4, 8, 12, 16, 24, 36, and 52.
Time Frame	12 weeks from the start date ( up until 52 weeks)

Outcome Measure Data

Analysis Population Description

The efficacy analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (overall evaluation by the physician based upon change in clinical symptoms and laboratory findings) at least once. Of the participants included in the efficacy analysis set (n=1312), 1259 participants had available data at baseline.

Arm/Group Title	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride)
Arm/Group Description	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.
Measure Participants	1259
Week 4 (n=468)	-6.0 (6.6)
Week 8 (n=290)	-9.1 (7.4)
Week 12 (n=667)	-12.3 (7.6)
Week 16 (n=233)	-11.2 (8.2)
Week 24 (n=124)	-12.0 (8.1)
Week 36 (n=116)	-12.2 (8.8)
Week 52 (n=527)	-15.2 (9.1)

3. Secondary Outcome

Title	Change From Baseline in the Montgomery - Asberg Depression Rating Scale (MADRS) Total Scores at Pre-specified Evaluation Points
Description	MADRS is a clinician-administered rating scale that assesses the overall severity of depressive symptoms. The MADRS had a 10-item checklist (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Items are scored from 0 to 6, and the total score ranges from 0 to 60, higher scores indicating more severity. Change from baseline: mean score at observation minus mean score at baseline. Evaluation was performed at Week 4, 8, 12, 16, 24, 36, and 52.
Time Frame	12 weeks from the start date ( up until 52 weeks)

Outcome Measure Data

Analysis Population Description

The efficacy analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (overall evaluation by the physician based upon change in clinical symptoms and laboratory findings) at least once. Of the participants included in the efficacy analysis set (n=1312), 902 participants had available data at baseline.

Arm/Group Title	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride)
Arm/Group Description	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.
Measure Participants	902
Week 4 (n=298)	-7.5 (9.0)
Week 8 (n=175)	-11.6 (10.7)
Week 12 (n=501)	-15.4 (9.6)
Week 16 (n=173)	-15.0 (11.0)
Week 24 (n=93)	-13.9 (10.0)
Week 36 (n=81)	-15.7 (10.6)
Week 52 (n=414)	-19.6 (10.9)

4. Secondary Outcome

Title	Clinical Global Impressions-Severity
Description	CGI-S is a 7-point clinician-administered rating scale that assesses overall severity of the current illness state. The score ranges from 1 to 7, higher scores indicating more affected: "1: normal, not at all ill," "2: borderline mentally ill," "3: mildly ill," "4: moderately ill," "5: markedly ill," "6: severely ill," or "7: among the most extremely ill patients." Evaluation was performed at Week 4, 8, 12, 16, 24, 36, and 52.
Time Frame	12 weeks from the start date (up until 52 weeks)

Outcome Measure Data

Analysis Population Description

The efficacy analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (overall evaluation by the physician based upon change in clinical symptoms and laboratory findings) at least once. Of the participants included in the efficacy analysis set (n=1312), a cross tabulation of the patients with available baseline CGI-S scores by CGI-S scores Week 12 and Week 52 is described.

Arm/Group Title	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride) Baseline 1	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride) Baseline 2	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride) Baseline 3	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride) Baseline 4	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride) Baseline 5	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride) Baseline 6	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride) Baseline 7
Arm/Group Description	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.
Measure Participants	1	7	182	590	285	104	4
Week 12 1: Normal, not at all ill	0 0%	2 NaN	19 NaN	56 NaN	9 NaN	7 NaN	1 NaN
Week 12 2: Borderline mentally ill	0 0%	1 NaN	45 NaN	98 NaN	38 NaN	15 NaN	1 NaN
Week 12 3: Mildly ill	0 0%	0 NaN	24 NaN	133 NaN	52 NaN	10 NaN	0 NaN
Week 12 4: Moderately ill	0 0%	0 NaN	2 NaN	45 NaN	61 NaN	10 NaN	0 NaN
Week 12 5: Markedly ill	0 0%	0 NaN	0 NaN	2 NaN	13 NaN	7 NaN	0 NaN
Week 12 6: Severely ill	0 0%	0 NaN	0 NaN	0 NaN	1 NaN	5 NaN	0 NaN
Week 12 7: Among the most extremely ill patients	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Week 52 1: Normal, not at all ill	0 0%	0 NaN	27 NaN	76 NaN	40 NaN	16 NaN	1 NaN
Week 52 2: Borderline mentally ill	0 0%	2 NaN	33 NaN	92 NaN	47 NaN	14 NaN	0 NaN
Week 52 3: Mildly ill	0 0%	0 NaN	15 NaN	69 NaN	39 NaN	7 NaN	0 NaN
Week 52 4: Moderately ill	0 0%	0 NaN	0 NaN	21 NaN	14 NaN	2 NaN	0 NaN
Week 52 5: Markedly ill	0 0%	0 NaN	0 NaN	2 NaN	5 NaN	1 NaN	0 NaN
Week 52 6: Severely ill	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	4 NaN	0 NaN
Week 52 7: Among the most extremely ill patients	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN

5. Secondary Outcome

Title	Changes in the Clinical Global Impressions-Improvement
Description	CGI-I is a 7-point clinician-administered rating scale that assesses overall improvement of the disease/condition. The score ranges from 1 to 7, higher scores indicating more affected: was assessed as "1: markedly improved," "2: moderately improved," "3: mildly improved," "4: no change," "5: slightly worsened," "6: worsened," or "7: severely worsened." Evaluation was performed at Week 4, 8, 12, 16, 24, 36, and 52.
Time Frame	12 weeks from the start date (up until 52 weeks)

Outcome Measure Data

Analysis Population Description

The efficacy analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (overall evaluation by the physician based upon change in clinical symptoms and laboratory findings) at least once. Of the participants included in the efficacy analysis set (n=1312), those who had available data at Week 12 and 52 were evaluated.

Arm/Group Title	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride) Week 12	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride) Week 52
Arm/Group Description	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.
Measure Participants	664	533
1: Markedly improved	199 14.9%	235 NaN
2: Moderately improved	175 13.1%	178 NaN
3: Mildly improved	212 15.9%	88 NaN
4: No change	70 5.2%	28 NaN
5: Slightly worsened	5 0.4%	3 NaN
6: Worsened	3 0.2%	1 NaN
7: Severely worsened	0 0%	0 NaN

Adverse Events

Time Frame	12 weeks from the start date (up until 52 weeks)
Adverse Event Reporting Description	The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both serious and non-serious events during the study.
Arm/Group Title	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride)
Arm/Group Description	Participants who received Effexor as indicated in the approved local product document were observed for a period of 12 weeks from the start date (up until 52 weeks). The dosage can be adjusted as per physician's discretion.
All Cause Mortality
	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride)
	Affected / at Risk (%)	# Events
Total	0/1334 (0%)
Serious Adverse Events
	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride)
	Affected / at Risk (%)	# Events
Total	20/1334 (1.5%)
Gastrointestinal disorders
Alcoholic pancreatitis	1/1334 (0.1%)
Hepatobiliary disorders
Jaundice cholestatic	1/1334 (0.1%)
Liver disorder	1/1334 (0.1%)
Immune system disorders
Anaphylactic shock	1/1334 (0.1%)
Infections and infestations
Pneumonia	1/1334 (0.1%)
Injury, poisoning and procedural complications
Meniscus injury	1/1334 (0.1%)
Subdural haematoma	1/1334 (0.1%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	1/1334 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile duct cancer	1/1334 (0.1%)
Gastric cancer	1/1334 (0.1%)
Leukaemia	1/1334 (0.1%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/1334 (0.1%)
Psychiatric disorders
Completed suicide	1/1334 (0.1%)
Depression	2/1334 (0.1%)
Depressive symptom	1/1334 (0.1%)
Hypomania	1/1334 (0.1%)
Mania	1/1334 (0.1%)
Suicidal ideation	2/1334 (0.1%)
Suicide attempt	1/1334 (0.1%)
Other (Not Including Serious) Adverse Events
	EFFEXOR SR CAPSULES (Venlafaxine Hydrochloride)
	Affected / at Risk (%)	# Events
Total	495/1334 (37.1%)
Cardiac disorders
Palpitations	13/1334 (1%)
Ear and labyrinth disorders
Tinnitus	3/1334 (0.2%)
Gastrointestinal disorders
Abdominal discomfort	5/1334 (0.4%)
Abdominal pain	3/1334 (0.2%)
Abdominal pain upper	5/1334 (0.4%)
Constipation	36/1334 (2.7%)
Diarrhoea	10/1334 (0.7%)
Eructation	2/1334 (0.1%)
Gastritis	3/1334 (0.2%)
Gastrointestinal disorder	2/1334 (0.1%)
Nausea	76/1334 (5.7%)
Vomiting	7/1334 (0.5%)
General disorders
Chest pain	2/1334 (0.1%)
Feeling abnormal	3/1334 (0.2%)
Malaise	26/1334 (1.9%)
Thirst	5/1334 (0.4%)
Withdrawal syndrome	2/1334 (0.1%)
Hepatobiliary disorders
Hepatic function abnormal	12/1334 (0.9%)
Hepatic steatosis	2/1334 (0.1%)
Liver disorder	3/1334 (0.2%)
Infections and infestations
Gastroenteritis	2/1334 (0.1%)
Nasopharyngitis	2/1334 (0.1%)
Investigations
Blood pressure increased	6/1334 (0.4%)
Weight increased	3/1334 (0.2%)
Metabolism and nutrition disorders
Decreased appetite	13/1334 (1%)
Dyslipidaemia	2/1334 (0.1%)
Hypercholesterolaemia	3/1334 (0.2%)
Hyperlipidaemia	4/1334 (0.3%)
Hyperphagia	2/1334 (0.1%)
Musculoskeletal and connective tissue disorders
Neck pain	2/1334 (0.1%)
Nervous system disorders
Akathisia	2/1334 (0.1%)
Dizziness	25/1334 (1.9%)
Dysgeusia	2/1334 (0.1%)
Headache	23/1334 (1.7%)
Hypersomnia	5/1334 (0.4%)
Hypoaesthesia	2/1334 (0.1%)
Migraine	2/1334 (0.1%)
Somnolence	53/1334 (4%)
Tremor	3/1334 (0.2%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	3/1334 (0.2%)
Psychiatric disorders
Anger	2/1334 (0.1%)
Anxiety	3/1334 (0.2%)
Hallucination, auditory	3/1334 (0.2%)
Hypomania	5/1334 (0.4%)
Initial insomnia	4/1334 (0.3%)
Insomnia	39/1334 (2.9%)
Intentional self-injury	3/1334 (0.2%)
Irritability	2/1334 (0.1%)
Libido decreased	2/1334 (0.1%)
Mania	5/1334 (0.4%)
Middle insomnia	6/1334 (0.4%)
Sleep disorder	5/1334 (0.4%)
Suicidal ideation	5/1334 (0.4%)
Renal and urinary disorders
Dysuria	6/1334 (0.4%)
Pollakiuria	2/1334 (0.1%)
Urinary incontinence	2/1334 (0.1%)
Reproductive system and breast disorders
Ejaculation disorder	3/1334 (0.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/1334 (0.1%)
Skin and subcutaneous tissue disorders
Eczema	3/1334 (0.2%)
Hyperhidrosis	7/1334 (0.5%)
Night sweats	3/1334 (0.2%)
Vascular disorders
Hypertension	2/1334 (0.1%)
Orthostatic hypotension	2/1334 (0.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.