Safety And Efficacy Of Maraviroc In Patients For HIV Patients (Regulatory Post Marketing Commitment Plan)

DRUG USE INVESTIGATION FOR HIV INFECTION PATIENTS OF MARAVIROC (REGULATORY POST MARKETING COMMITMENT PLAN).

The objective of this surveillance is to collect information about 1) adverse drug reaction not expected from the LPD (unknown adverse drug reaction), 2) the incidence of adverse drug reactions in this surveillance, and 3)factors considered to affect the safety and/or efficacy of this drug.

Study Overview

• Status: Completed
• Conditions: CCR5-tropic HIV-1 Infection
• Intervention / Treatment: Drug: CELSENTRI® Tablets

Detailed Description

All the patients whom an investigator prescribes the first CELSENTRI® Tablets should be registered consecutively until the number of subjects reaches target number in order to extract patients enrolled into the investigation at random.

• Study Type: Observational
• Enrollment (Actual): 68

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The patients whom an investigator involving A4001093 prescribes the Maraviroc Tablets (CELSENTRI® Tablets).

Description

Inclusion Criteria:

Patients need to be administered CELSENTRI® Tablets in order to be enrolled in the surveillance.

Exclusion Criteria:

Patients not administered CELSENTRI® Tablets.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Maraviroc Tablets; Patients administered.

Drug: CELSENTRI® Tablets; CELSENTRI ® Tablets 150mg, depending on the Investigator prescription. Frequency and duration are according to Package Insert as follows. "The usual adult dosage is 300 mg twice daily. Maraviroc must be used in combination with other anti-HIV drugs. The dosage may be adjusted according to co-administered medical products. Maraviroc can be taken with or without food".; Other Names: CELSENTRI® Tablets, maraviroc, Selzentry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Drug Reactions (ADRs)	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Number of Participants With Unknown Adverse Drug Reactions (ADRs)	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. Unknown ADRs were the ADRs those were not listed on the package insert.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Gender	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by gender are reported to assess gender as a risk factor for ADR.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Age	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by age are reported to assess age as a risk factor for ADR. ">=" refers to greater than or equal to.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Inpatient or Outpatient Status	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by inpatient or outpatient status are reported to assess inpatient or outpatient status as a risk factor for ADR.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Ethnicity	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by ethnicity are reported to assess ethnicity as a risk factor for ADR.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Primary: Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Presence or Absence of History of Therapies for Human Immuno-Deficiency Virus (HIV) Infection	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by presence or absence of history of therapies for HIV Infection are reported to assess presence or absence of history of therapies for HIV Infection as a risk factor for ADR.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor HIV Infection Duration	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by HIV infection duration are reported to assess HIV infection duration as a risk factor for ADR. Unknown: participants for which the duration of HIV infection was not known.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Presence or Absence of Allergies	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by presence or absence of allergies are reported to assess presence or absence of allergies as a risk factor for ADR. Unknown: participants for which the presence or absence of allergies was not known.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Presence or Absence of Comorbidities	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by presence or absence of comorbidities are reported to assess presence or absence of comorbidities as a risk factor for ADR. Comorbidity referred to the presence of co-existing or additional diseases along with HIV infection.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Presence or Absence of Renal Impairment	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by presence or absence of renal impairment are reported to assess presence or absence of renal impairment as a risk factor for ADR.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Presence or Absence of Hepatic Impairment	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by presence or absence of hepatic impairment are reported to assess presence or absence of hepatic impairment as a risk factor for ADR.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Presence or Absence of Hemophilia	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by presence or absence of hemophilia are reported to assess presence or absence of hemophilia as a risk factor for ADR. Hemophilia is a bleeding disorder that slows the blood clotting process. Participants with this condition experience prolonged bleeding or oozing following an injury, surgery, or having a tooth pulled.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Mean Daily Dose of Celsentri	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by mean daily dose of Celsentri are reported to assess mean daily dose of Celsentri as a risk factor for ADR. One tablet of Celsentri had a dose of 150 mg.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Number of Concomitant Anti-HIV Drugs Use	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by number of concomitant anti-HIV treatment are reported to assess number of concomitant anti-HIV treatment as a risk factor for ADR. Concomitant drugs refers to the drugs other than Celsentri.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Centers for Disease Control and Prevention (CDC) Classification	An ADR:any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by physician.Participants are divided into 3 categories as per CDC classification based on level of HIV infection: Category A= asymptomatic HIV-1 infection, persistent generalized lymphadenopathy and acute(primary)HIV-1 infection with accompanying illness or history of acute HIV-1 infection in adult or adolescent aged>=13 years, Category B: conditions attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or the conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection in an HIV-infected adolescent or adult; and Category C: clinical conditions listed in the acquired immunodeficiency syndrome (AIDS) diagnostic criteria, corresponding to conventional AIDS. Unknown: Participants for which CDC classification was not described.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor as Per Presence or Absence of Concomitant Therapies	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by presence or absence of concomitant therapies are reported to assess presence or absence of concomitant therapies as a risk factor for ADR. Concomitant therapies were the treatments taken by participants to treat comorbid conditions.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Presence or Absence of Use of Cytochrome P450 3A4 (CYP3A4) Enzyme Inducer Taken Along With Celsentri	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by presence or absence of concomitant CYP3A4 enzyme inducer use are reported to assess presence or absence of concomitant CYP3A enzyme inducer use as a risk factor for ADR. CYP3A4 is an important enzyme in the body, mainly found in the liver and in the intestine. This enzyme is responsible for metabolism of majority of drugs. Many of the food substances and commonly used drugs act as inducer for enzyme CYP3A4.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Total Number of Days of Administration of Celsentri	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by total number of days of administration of Celsentri are reported to assess total number of days of administration of Celsentri as a risk factor for ADR.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Percentage of Participants With Adverse Drug Reactions (ADRs): Factor Mean Total Dose of Celsentri	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician. In this outcome measure percentage of participants with ADRs categorized by mean total dose of Celsentri are reported to assess mean total dose of Celsentri as a risk factor for ADR. One tablet of Celsentri had a dose of 150 mg.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Number of Adverse Drug Reactions (ADRs) Considered to Have Occurred Due to Effect of Celsentri on Immune Function	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Number of Adverse Drug Reactions (ADRs) Considered to Have Occurred Due to Effect of Celsentri on Hepatic Function	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Number of Adverse Drug Reactions (ADRs) Considered to Have Occurred Due to Effect of Celsentri on Cardiovascular Effects	An ADR was any untoward medical occurrence attributed to Celsentri tablets in a participant who received Celsentri tablets. Relatedness to Celsentri tablets was assessed by the physician.	From April 2009 to December 2018 (up to approximately 8 years 8 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Number of Plasma Human Immuno-Deficiency Virus-Ribosomal Ribonucleic Acid (HIV-RNA) Copies: Factor Gender	HIV-RNA copy numbers were measured employing the TaqMan assay with the lower limit of detection of 40 copies per milliliter (copies/mL). The reported data for plasma HIV-RNA copies was calculated after logarithmic conversion.	Month 0 (Baseline), 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84
Mean Number of Cluster of Differentiation of More Than 4 (CD4+) Lymphocyte Count: Factor Gender	CD4+ Lymphocyte were counted by CD4 cells per cubic millimeter (cells/mm^3). CD4 cells are the white blood cells and act as laboratory marker providing an indication of immune functioning. A higher number is associated with better immune functioning.	Month 0 (Baseline), 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84
Mean Number of Plasma Human Immuno-Deficiency Virus-Ribosomal Ribonucleic Acid (HIV-RNA) Copies: Factor The Presence or Absence of Comorbidities	HIV-RNA copy numbers were measured employing the TaqMan assay with the lower limit of detection of 40 copies/mL. The reported data for plasma HIV-RNA copies was calculated after logarithmic conversion.	Month 0 (Baseline), 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84
Mean Number of CD4+ Lymphocyte Counts: Fcator The Presence or Absence of Comorbidities	CD4 cells are the white blood cells and act as laboratory marker providing an indication of immune functioning. A higher number is associated with better immune functioning.	Month 0 (Baseline), 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84
Mean Number of Plasma HIV-RNA Copies: Factor The Centers for Disease Control and Prevention (CDC) Classification	Participants are divided into 3 categories as per CDC classification based on the level of HIV infection as follows: Category A= asymptomatic HIV-1 infection, persistent generalized lymphadenopathy and acute (primary) HIV-1 infection with accompanying illness or history of acute HIV-1 infection in an adult or adolescent aged >=13 years, Category B: conditions attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or the conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection in an HIV-infected adolescent or adult; and Category C: clinical conditions listed in the acquired immunodeficiency syndrome (AIDS) diagnostic criteria, corresponding to conventional AIDS. Once criteria C has occurred, the person will remain in Category C even if symptoms are alleviated.	Month 0 (Baseline), 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84
Mean Number of CD4+ Lymphocyte Counts: Factor The Centers for Disease Control and Prevention (CDC) Classification	CD4 cells are the white blood cells and act as a laboratory marker providing an indication of immune functioning. A higher number is associated with better immune functioning. Participants are divided into 3 categories as per CDC classification based on the level of HIV infection as: Category A= asymptomatic HIV-1 infection, persistent generalized lymphadenopathy and acute(primary)HIV-1 infection with accompanying illness or history of acute HIV-1 infection in an adult or adolescent aged>=13 years, Category B: conditions attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or the conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection in an HIV-infected adolescent or adult; and Category C: clinical conditions listed in the AIDS diagnostic criteria, corresponding to conventional AIDS. Once criteria C has occurred, the person will remain in Category C even if symptoms are alleviated.	Month 0 (Baseline), 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84
Mean Number of Plasma HIV-RNA Copies: Factor The Presence or Absence of History of Therapies for HIV Infection	HIV-RNA copy numbers were measured employing the TaqMan assay with the lower limit of detection of 40 copies/mL. The reported data for plasma HIV-RNA copies was calculated after logarithmic conversion.	Month 0 (Baseline), 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84
Mean Number of CD4+ Lymphocyte Counts: Factor Presence or Absence of History of Therapies for HIV Infection	CD4 cells are the white blood cells and act as a laboratory marker providing an indication of immune functioning. A higher number is associated with better immune functioning.	Month 0 (Baseline), 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84
Mean Number of Plasma HIV-RNA Copies: Factor The Presence or Absence of Use of Cytochrome P450 3A4 (CYP3A4) Enzyme Inducer Taken Along With Celsentri	HIV-RNA copy numbers were measured employing the TaqMan assay with the lower limit of detection of 40 copies/mL. CYP3A4 is an important enzyme in the body, mainly found in the liver and in the intestine. This enzyme is responsible for metabolism of majority of drugs. Many of the food substances and commonly used drugs act as inducers of enzyme CYP3A4. The reported data for plasma HIV-RNA copies was calculated after logarithmic conversion.	Month 0 (Baseline), 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84
Mean Number of CD4+ Lymphocyte: Factor The Presence or Absence of Use of Cytochrome P450 3A4 (CYP3A4) Enzyme Inducer Taken Along With Celsentri	CD4 cells are the white blood cells and act as laboratory marker providing an indication of immune functioning. A higher number is associated with better immune functioning. CYP3A4 is an important enzyme in the body, mainly found in the liver and in the intestine. This enzyme is responsible for metabolism of many of drugs. Many of the food substances and commonly used drugs act as inducers of enzyme CYP3A4.	Month 0 (Baseline), 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84
Number of Participants With Tropism Switch From CCR5- to CXCR4-Tropic Variants	CCR5= C-C chemokine receptor type 5 and CXCR4= C-X-C chemokine receptor type 4. Tropism switch is the mutation of CCR5-tropic HIV-1 to a CXCR4-using virus.	From April 2009 to December 2018 (up to approximately 8 years 8 months)
Mean Number of Plasma HIV-RNA Copies for Participants Who Took Concomitant Therapies Along With Celsentri		Month 0 (Baseline), 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, 57, 60, 63, 66, 69, 72, 75, 78, 81 and 84

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 31, 2010
• Primary Completion (ACTUAL): December 24, 2018
• Study Completion (ACTUAL): December 24, 2018

Study Registration Dates

• First Submitted: March 17, 2009
• First Submitted That Met QC Criteria: March 17, 2009
• First Posted (ESTIMATE): March 18, 2009

Study Record Updates

• Last Update Posted (ACTUAL): January 2, 2020
• Last Update Submitted That Met QC Criteria: December 6, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc
• Other Study ID Numbers: A4001093

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No