HEPSERA PMS: HEPSERA Post Marketing Surveillance

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01329419
• Collaborator: (none)
• Enrollment: 4,393
• Duration (Months): 66

Study Details

Study Description

Brief Summary

An open label, multi-centre, non-interventional post-marketing surveillance to monitor the safety and/or efficacy of adefovir dipivoxil administered in Korean CHB patients according to the prescribing information

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B	Drug: adefovir dipivoxil

Detailed Description

This study is a post-marketing surveillance to monitor safety and efficacy of adefovir dipivoxil and identify SAEs, adverse drug reactions (ADRs), and unexpected AEs not described as precautions or warnings and to identify possible factors that have an effect on the AEs and to assess effectiveness of adefovir dipivoxil in real clinical practices after marketing. The subjects are patients prescribed for adefovir dipivoxil by the investigators at the sites based on prescription information in normal clinical practices.

Study Design

• Study Type: Observational
• Actual Enrollment: 4393 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: A Post-marketing Surveillance to Monitor the Safety of HEPSERA(Adefovir Dipivoxil 10mg) Adminstered in Korean Subjects According to the Prescribing Information
• Study Start Date: Aug 1, 2004
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
adefovir dipivoxil Patients administrated adefovir at the site	Drug: adefovir dipivoxil; Basically there is no treatment allocation. Subjects who would be administered of adefovir at their physicians' discretion will be enrolled. Dosage regimen will be recommended according to the prescribing information. Subjects will be enrolled consecutively.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With an Adverse Event [12 weeks]

   An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. For a list of all adverse events occurring during the course of the study, please see the table entitled "Other (non-serious) adverse events" in the Adverse Event section of the results record.

Secondary Outcome Measures

1. Number of Participants With a Serious Adverse Event [12 weeks]

   A serious adverse event is any untoward medical occurrence that, at any dose: results in death /is life-threatening; requires hospitalization or prolongation of exixting hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is another medically significant event. For a list of all serious adverse events occurring during the course of the study, please see the table entitled "Serious Adverse Events" in the Adverse Event section of the results record.

2. Number of Participants With the Indicated Unexpected Adverse Events [12 weeks]

   An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Unexpected adverse events include those not listed in the approved product information and not described as precautions or warnings.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients administrated adefovir dipivoxil at the site

Exclusion Criteria:

• Patients administrated adefovir dipivoxil before center initiated date

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01329419
• Other Study ID Numbers: 105711
• First Posted: Apr 5, 2011
• Last Update Posted: Jul 5, 2017
• Last Verified: Jun 1, 2017

• Additional relevant MeSH terms: Hepatitis B; Adefovir; Adefovir dipivoxil

Study Results

Participant Flow

Recruitment Details	The objective of this post-marketing surveillance (PMS) study was to monitor the safety and efficacy of Hepsera in the real clinical setting after launch.

Arm/Group Title	Hepsera 10 mg Once a Day
Arm/Group Description	Hepsera tablet containing 10 milligrams (mg) of adefovir dipivoxil administered once daily
Period Title: Overall Study
STARTED	4393
COMPLETED	4158
NOT COMPLETED	235

Baseline Characteristics

Arm/Group Title	Hepsera 10 mg Once a Day
Arm/Group Description	Hepsera tablet containing 10 milligrams (mg) of adefovir dipivoxil administered once daily
Overall Participants	4158
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.9 (11)
Sex/Gender, Customized (Number) [Number]
Female	874 21%
Male	3280 78.9%
Missing	4 0.1%
Race/Ethnicity, Customized (participants) [Number]
Korean	4158 100%
Not Korean	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With an Adverse Event
Description	An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. For a list of all adverse events occurring during the course of the study, please see the table entitled "Other (non-serious) adverse events" in the Adverse Event section of the results record.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who had been administered the investigational drug at least once and had undergone all safety assessments

Arm/Group Title	Hepsera 10 mg Once a Day
Arm/Group Description	Hepsera tablet containing 10 milligrams (mg) of adefovir dipivoxil administered once daily
Measure Participants	4158
Number [participants]	74 1.8%

2. Secondary Outcome

Title	Number of Participants With a Serious Adverse Event
Description	A serious adverse event is any untoward medical occurrence that, at any dose: results in death /is life-threatening; requires hospitalization or prolongation of exixting hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is another medically significant event. For a list of all serious adverse events occurring during the course of the study, please see the table entitled "Serious Adverse Events" in the Adverse Event section of the results record.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Hepsera 10 mg Once a Day
Arm/Group Description	Hepsera tablet containing 10 mg of adefovir dipivoxil administered once daily
Measure Participants	4158
Number [participants]	32 0.8%

3. Secondary Outcome

Title	Number of Participants With the Indicated Unexpected Adverse Events
Description	An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Unexpected adverse events include those not listed in the approved product information and not described as precautions or warnings.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Hepsera 10 mg Once a Day
Arm/Group Description	Hepsera tablet containing 10 mg of adefovir dipivoxil administered once daily
Measure Participants	4158
Sputum Increased	5 0.1%
Hepatic Cirrhosis	4 0.1%
Hepatic Encephalopathy	2 0%
Hepatic Neoplasm	7 0.2%
Hypoaesthesia	2 0%
Hemoptysis	1 0%
Azotaemia	1 0%
Marrow Hyperplasia	1 0%
Marrow Depression	1 0%
Fracture	1 0%
Fasciitis Necrotising	1 0%
Skin Reaction Localised	1 0%
Myalgia	1 0%
Resistance	1 0%
Proteinuria	1 0%
Edema Peripheral	1 0%
Dysuria	2 0%
Pancytopenia	1 0%
Ascites	3 0.1%
Splenomegaly	1 0%
Hernia Inguinal	1 0%
Esophageal Varices	1 0%
Urethral Disorder	1 0%
Erythrocytes Abnormal	1 0%
Vein Varicose	4 0.1%
Hemorrhage Rectum	1 0%
Gastric Ulcer Hemorrhagic	1 0%
Hematemesis	1 0%
Pneumonia	2 0%
Pulmonary Carcinoma	1 0%
Fatigue	3 0.1%
Dyspnea	1 0%
Jaundice	2 0%
Melaena	1 0%

Adverse Events

Time Frame	February 19, 2004 to February 18, 2010
Adverse Event Reporting Description	Adverse events were coded by using World Health Organization Adverse Reactions Terminology (WHOART, preferred term level) according to the local regulation.
Arm/Group Title	Hepsera 10 mg Once a Day
Arm/Group Description	Hepsera tablet containing 10 milligrams (mg) of adefovir dipivoxil administered once daily
All Cause Mortality
	Hepsera 10 mg Once a Day
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Hepsera 10 mg Once a Day
	Affected / at Risk (%)	# Events
Total	32/4158 (0.8%)
Blood and lymphatic system disorders
Vein Varicose	3/4158 (0.1%)
Pancytopenia	1/4158 (0%)
Gastrointestinal disorders
Gastric Ulcer Hemorrhagic	1/4158 (0%)
Melaena	1/4158 (0%)
Hematemesis	1/4158 (0%)
Abdominal Pain	2/4158 (0%)
General disorders
Fever	1/4158 (0%)
Ascites	1/4158 (0%)
Hepatobiliary disorders
Hepatic Failure	9/4158 (0.2%)
Hepatic Cirrhosis	4/4158 (0.1%)
Hepatic Encephalopathy	2/4158 (0%)
Jaundice	2/4158 (0%)
Alanine Transaminase/Aspartate Aminotransferase Increased	1/4158 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	1/4158 (0%)
Fracture	1/4158 (0%)
Fasciitis Necrotising	1/4158 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic Neoplasm	7/4158 (0.2%)
Pulmonary Carcinoma	1/4158 (0%)
Nervous system disorders
Hypoaesthesia	1/4158 (0%)
Reproductive system and breast disorders
Hernia Inguinal	1/4158 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/4158 (0%)
Pneumonia	2/4158 (0%)
Skin and subcutaneous tissue disorders
Rash	1/4158 (0%)
Other (Not Including Serious) Adverse Events
	Hepsera 10 mg Once a Day
	Affected / at Risk (%)	# Events
Total	74/4158 (1.8%)
Blood and lymphatic system disorders
Vein Varicose	4/4158 (0.1%)
Red Blood Cell Abnormality	1/4158 (0%)
Marrow Hyperplasia	1/4158 (0%)
Marrow Depression	1/4158 (0%)
Pancytopenia	1/4158 (0%)
Splenomegaly	1/4158 (0%)
Gastrointestinal disorders
Abdominal Pain	6/4158 (0.1%)
Dyspepsia	5/4158 (0.1%)
Gagging	4/4158 (0.1%)
Flatulence	4/4158 (0.1%)
Esophageal Varices	1/4158 (0%)
Hemorrhage Rectum	1/4158 (0%)
Gastric Ulcer Hemorrhagic	1/4158 (0%)
Hematemesis	1/4158 (0%)
Melaena	1/4158 (0%)
General disorders
Diarrhea	2/4158 (0%)
Asthenia	5/4158 (0.1%)
Ascites	3/4158 (0.1%)
Fatigue	3/4158 (0.1%)
Tolerance	1/4158 (0%)
Edema Peripheral	1/4158 (0%)
Fever	1/4158 (0%)
Hepatobiliary disorders
Hepatic Failure	9/4158 (0.2%)
Hepatic Cirrhosis	4/4158 (0.1%)
Alanine Transaminase/Aspartate Aminotransferase Increased	2/4158 (0%)
Hepatic Encephalopathy	2/4158 (0%)
Hepatitis Chronic Active Aggrava	2/4158 (0%)
Jaundice	2/4158 (0%)
Musculoskeletal and connective tissue disorders
Fracture	1/4158 (0%)
Fasciitis Necrotising	1/4158 (0%)
Myalgia	1/4158 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic Neoplasm	7/4158 (0.2%)
Pulmonary Carcinoma	1/4158 (0%)
Nervous system disorders
Hypoaesthesia	2/4158 (0%)
Headache	1/4158 (0%)
Renal and urinary disorders
Dysuria	2/4158 (0%)
Azotaemia	1/4158 (0%)
Proteinuria	1/4158 (0%)
Urethral Disorder	1/4158 (0%)
Hematuria	1/4158 (0%)
Hernia Inguinal	1/4158 (0%)
Respiratory, thoracic and mediastinal disorders
Coughing	7/4158 (0.2%)
Sputum Increased	5/4158 (0.1%)
Pneumonitis	2/4158 (0%)
Hemoptysis	1/4158 (0%)
Pharyngitis	1/4158 (0%)
Dyspnea	1/4158 (0%)
Skin and subcutaneous tissue disorders
Rash	3/4158 (0.1%)
Pruritus	1/4158 (0%)
Skin Reaction Localised	1/4158 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.