Temodal (Temozolomide) Post Marketing Surveillance Protocol (Study P05557AM2)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00723827
• Collaborator: (none)
• Enrollment: 682
• Duration (Months): 42

Study Details

Study Description

Brief Summary

The purpose of this surveillance is to evaluate the postmarketing safety and efficacy of Temodal capsule (temozolomide) under actual conditions of use, and to understand some of the following points that are in question and doubt:

• Incidence of adverse events under actual conditions of use (Serious and Nonserious Adverse Events);

• Adverse Drug Reactions not shown in the directions for use (will be stated as Unexpected Adverse Reaction);

• Adverse Event caused by misuse, abuse, or drug interactions;

• Other information concerned with safety or efficacy.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma; Glioma; Astrocytoma	Drug: Temozolomide; Radiation: Radiotherapy

Study Design

• Study Type: Observational
• Actual Enrollment: 682 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Temodal (Temozolomide) Post Marketing Surveillance Protocol
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
All Participants Participants with newly diagnosed glioblastoma multiforme (treat with temozolomide & radiotherapy) or participants with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy (treat with temozolomide).	Drug: Temozolomide; Administration of temozolomide based on the product labeling.; Other Names: Temodal Temodar SCH 052365 MK-7365 ; Radiation: Radiotherapy; Radiotherapy given concomitantly with temozolomide for newly diagnosed glioblastoma multiforme.; Other Names: Radiation therapy irradiation

Outcome Measures

Primary Outcome Measures

1. Number of Participants Experiencing Adverse Events (AEs) [Complete study duration & 30 days after completion (up to approximately 7.5 months)]

   An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of vaccine, whether or not considered related to the medicinal product.

2. Number of Participants Experiencing Unexpected Adverse Drug Reactions (ADRs) [Complete study duration & 30 days after completion (up to approximately 7.5 months)]

   An unexpected ADR was defined as an adverse reaction, whose nature, severity, specificity, or outcome is not consistent with the term or description used in the applicable product information.

3. Number of Temozolomide Misuse or Abuse Events [Complete study duration & 30 days after completion (up to approximately 7.5 months)]

   Drug abuse was defined as the use of the study drug for a non-therapeutic effect. Misuse was defined as use of the study medication in a way that was not prescribed.

4. Number of Temozolomide Drug Interactions [Complete study duration & 30 days after completion (up to approximately 7.5 months)]

   Drug interaction was defined as a chemical or physiological reaction that can occur when two different drugs are taken together.

5. Efficacy: Number of Participants Experiencing Complete Response (CR), Partial Response (PR), or Stable Disease(SD) [Complete study duration (up to approximately 6.5 months)]

   The response ratings were based on the judgment of the investigator.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participants who are prescribed with temozolomide by local labeling:

• participants with newly diagnosed glioblastoma multiforme;

• participants with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy.

Exclusion Criteria:

• N/A

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00723827
• Other Study ID Numbers: P05557
• First Posted: Jul 29, 2008
• Last Update Posted: Jan 30, 2015
• Last Verified: Jan 1, 2015

• Additional relevant MeSH terms: Glioblastoma; Astrocytoma; Temozolomide

Study Results

Participant Flow

Arm/Group Title	All Participants
Arm/Group Description	Participants with newly diagnosed glioblastoma multiforme (treat with temozolomide & radiotherapy) or participants with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy (treat with temozolomide). Temozolomide : Administration of temozolomide based on the product labeling. Radiotherapy : Radiotherapy given concomitantly with temozolomide for newly diagnosed glioblastoma multiforme.
Period Title: Overall Study
STARTED	682
COMPLETED	682
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Participants with newly diagnosed glioblastoma multiforme (treat with temozolomide & radiotherapy) or participants with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy (treat with temozolomide). Temozolomide : Administration of temozolomide based on the product labeling. Radiotherapy : Radiotherapy given concomitantly with temozolomide for newly diagnosed glioblastoma multiforme.
Overall Participants	682
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.57 (13.86)
Sex: Female, Male (Count of Participants)
Female	297 43.5%
Male	385 56.5%
Region of Enrollment (participants) [Number]
Korea, Republic Of	682 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Experiencing Adverse Events (AEs)
Description	An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of vaccine, whether or not considered related to the medicinal product.
Time Frame	Complete study duration & 30 days after completion (up to approximately 7.5 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	Participants with newly diagnosed glioblastoma multiforme (treat with temozolomide & radiotherapy) or participants with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy (treat with temozolomide). Temozolomide : Administration of temozolomide based on the product labeling. Radiotherapy : Radiotherapy given concomitantly with temozolomide for newly diagnosed glioblastoma multiforme.
Measure Participants	682
Number [participants]	324 47.5%

2. Primary Outcome

Title	Number of Participants Experiencing Unexpected Adverse Drug Reactions (ADRs)
Description	An unexpected ADR was defined as an adverse reaction, whose nature, severity, specificity, or outcome is not consistent with the term or description used in the applicable product information.
Time Frame	Complete study duration & 30 days after completion (up to approximately 7.5 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	Participants with newly diagnosed glioblastoma multiforme (treat with temozolomide & radiotherapy) or participants with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy (treat with temozolomide). Temozolomide : Administration of temozolomide based on the product labeling. Radiotherapy : Radiotherapy given concomitantly with temozolomide for newly diagnosed glioblastoma multiforme.
Measure Participants	682
Number [participants]	49 7.2%

3. Primary Outcome

Title	Number of Temozolomide Misuse or Abuse Events
Description	Drug abuse was defined as the use of the study drug for a non-therapeutic effect. Misuse was defined as use of the study medication in a way that was not prescribed.
Time Frame	Complete study duration & 30 days after completion (up to approximately 7.5 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	Participants with newly diagnosed glioblastoma multiforme (treat with temozolomide & radiotherapy) or participants with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy (treat with temozolomide). Temozolomide : Administration of temozolomide based on the product labeling. Radiotherapy : Radiotherapy given concomitantly with temozolomide for newly diagnosed glioblastoma multiforme.
Measure Participants	682
Number [Events]	1

4. Primary Outcome

Title	Number of Temozolomide Drug Interactions
Description	Drug interaction was defined as a chemical or physiological reaction that can occur when two different drugs are taken together.
Time Frame	Complete study duration & 30 days after completion (up to approximately 7.5 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	Participants with newly diagnosed glioblastoma multiforme (treat with temozolomide & radiotherapy) or participants with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy (treat with temozolomide). Temozolomide : Administration of temozolomide based on the product labeling. Radiotherapy : Radiotherapy given concomitantly with temozolomide for newly diagnosed glioblastoma multiforme.
Measure Participants	682
Number [events]	5

5. Primary Outcome

Title	Efficacy: Number of Participants Experiencing Complete Response (CR), Partial Response (PR), or Stable Disease(SD)
Description	The response ratings were based on the judgment of the investigator.
Time Frame	Complete study duration (up to approximately 6.5 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	Participants with newly diagnosed glioblastoma multiforme (treat with temozolomide & radiotherapy) or participants with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy (treat with temozolomide). Temozolomide : Administration of temozolomide based on the product labeling. Radiotherapy : Radiotherapy given concomitantly with temozolomide for newly diagnosed glioblastoma multiforme.
Measure Participants	682
CR	82 12%
PR	143 21%
SD	322 47.2%

Adverse Events

Arm/Group Title	All Participants
Arm/Group Description	Participants with newly diagnosed glioblastoma multiforme (treat with temozolomide & radiotherapy) or participants with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy (treat with temozolomide). Temozolomide : Administration of temozolomide based on the product labeling. Radiotherapy : Radiotherapy given concomitantly with temozolomide for newly diagnosed glioblastoma multiforme.
All Cause Mortality
	All Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	103/682 (15.1%)
Blood and lymphatic system disorders
EOSINOPHILIA	1/682 (0.1%)	1
LEUKOPENIA	2/682 (0.3%)	2
NEUTROPENIA	4/682 (0.6%)	4
PANCYTOPENIA	2/682 (0.3%)	2
THROMBOCYTOPENIA	2/682 (0.3%)	2
Cardiac disorders
CARDIAC ARREST	2/682 (0.3%)	2
MYOCARDIAL ISCHAEMIA	1/682 (0.1%)	1
Eye disorders
VISION BLURRED	1/682 (0.1%)	1
VISUAL IMPAIRMENT	1/682 (0.1%)	1
Gastrointestinal disorders
DIARRHOEA	1/682 (0.1%)	1
DYSPHAGIA	1/682 (0.1%)	1
HAEMORRHOIDS	1/682 (0.1%)	1
NAUSEA	2/682 (0.3%)	2
VOMITING	3/682 (0.4%)	3
General disorders
ASTHENIA	3/682 (0.4%)	3
CHEST DISCOMFORT	1/682 (0.1%)	1
CHILLS	1/682 (0.1%)	1
CONDITION AGGRAVATED	2/682 (0.3%)	2
DISEASE PROGRESSION	17/682 (2.5%)	17
FACE OEDEMA	1/682 (0.1%)	1
OEDEMA PERIPHERAL	1/682 (0.1%)	1
PYREXIA	7/682 (1%)	7
Hepatobiliary disorders
HEPATITIS	1/682 (0.1%)	1
HEPATITIS ACUTE	1/682 (0.1%)	1
Infections and infestations
APPENDICITIS	1/682 (0.1%)	1
CELLULITIS	1/682 (0.1%)	1
CENTRAL NERVOUS SYSTEM INFECTION	1/682 (0.1%)	1
HEPATITIS B	1/682 (0.1%)	1
LOCALISED INFECTION	1/682 (0.1%)	1
SEPSIS	2/682 (0.3%)	2
STAPHYLOCOCCAL INFECTION	1/682 (0.1%)	1
WOUND INFECTION	3/682 (0.4%)	3
Injury, poisoning and procedural complications
RADIATION NECROSIS	2/682 (0.3%)	2
SUBDURAL HAEMORRHAGE	2/682 (0.3%)	2
WOUND COMPLICATION	1/682 (0.1%)	1
Investigations
ALANINE AMINOTRANSFERASE INCREASED	4/682 (0.6%)	4
ASPARTATE AMINOTRANSFERASE INCREASED	4/682 (0.6%)	4
OXYGEN SATURATION DECREASED	1/682 (0.1%)	1
Metabolism and nutrition disorders
HYPERCALCAEMIA	1/682 (0.1%)	1
HYPERGLYCAEMIA	1/682 (0.1%)	1
METABOLIC ACIDOSIS	1/682 (0.1%)	1
Musculoskeletal and connective tissue disorders
BACK PAIN	1/682 (0.1%)	1
MUSCULAR WEAKNESS	1/682 (0.1%)	1
MUSCULOSKELETAL PAIN	1/682 (0.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO MENINGES	1/682 (0.1%)	1
METASTASES TO SPINE	2/682 (0.3%)	2
METASTATIC NEOPLASM	1/682 (0.1%)	1
NEOPLASM RECURRENCE	5/682 (0.7%)	5
Nervous system disorders
BRAIN OEDEMA	4/682 (0.6%)	4
CEREBRAL CYST	1/682 (0.1%)	1
CEREBRAL INFARCTION	1/682 (0.1%)	1
CONVULSION	9/682 (1.3%)	11
DEPRESSED LEVEL OF CONSCIOUSNESS	1/682 (0.1%)	1
DIZZINESS	2/682 (0.3%)	2
DYSARTHRIA	2/682 (0.3%)	2
HAEMORRHAGE INTRACRANIAL	1/682 (0.1%)	1
HEADACHE	5/682 (0.7%)	5
HYDROCEPHALUS	5/682 (0.7%)	5
INTRACRANIAL PRESSURE INCREASED	1/682 (0.1%)	1
MYELOPATHY	1/682 (0.1%)	1
PARTIAL SEIZURES	2/682 (0.3%)	2
SOMNOLENCE	2/682 (0.3%)	2
STUPOR	2/682 (0.3%)	2
Psychiatric disorders
CONFUSIONAL STATE	1/682 (0.1%)	1
Renal and urinary disorders
URINARY TRACT INFECTION	2/682 (0.3%)	2
RENAL FAILURE ACUTE	2/682 (0.3%)	2
Respiratory, thoracic and mediastinal disorders
PNEUMONIA	11/682 (1.6%)	11
ACUTE RESPIRATORY DISTRESS SYNDROME	2/682 (0.3%)	2
INTERSTITIAL LUNG DISEASE	1/682 (0.1%)	1
PLEURAL EFFUSION	1/682 (0.1%)	1
PNEUMONIA ASPIRATION	3/682 (0.4%)	3
PULMONARY EMBOLISM	2/682 (0.3%)	2
Vascular disorders
DEEP VEIN THROMBOSIS	2/682 (0.3%)	2
Other (Not Including Serious) Adverse Events
	All Participants
	Affected / at Risk (%)	# Events
Total	132/682 (19.4%)
Gastrointestinal disorders
NAUSEA	82/682 (12%)	101
VOMITING	54/682 (7.9%)	64
Metabolism and nutrition disorders
DECREASED APPETITE	46/682 (6.7%)	53

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The institution has the right to publish/present the study results. The institution agrees not to publish/present any interim results of the Study without the Sponsor's prior written consent. The institution further agrees to provide the Sponsor 30 days written notice prior to submission. The Sponsor has the right to review and comment. If the parties disagree, the institution agrees to meet with the Sponsor, prior to submission, to discuss and resolve any such issues or disagreement.