DRUG USE INVESTIGATION FOR HIV INFECTION PATIENTS OF MYCOBUTIN (REGULATORY POST MARKETING COMMITMENT PLAN).
Conditions: Non-tuberculous Mycobacterial Diseases, Tuberculosis, Inhibition of Disseminated Mycobacterium Avium Complex Disease Associated With HIV Infections
Sponsor: Pfizer

1
DRUG USE INVESTIGATION FOR HIV INFECTION PATIENTS OF MYCOBUTIN 
- HRD Joint Survey -
NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Mycobutin
A0061007   NON-INTERVENTIONAL STUDY PROTOCOL 
Final, Nov. 2015

2
Revised in November 2015
(For reexamination)
HRD Joint Survey: Protocol
Drugs for the treatment of HIV infection (anti-HIV drugs and drugs for the treatment of HIV-related diseases), which 
are currently subject to reexamination, have been approved based on the limited results of Japanese and overseas 
clinical trials due to the urgency of treatment for the target patients. Therefore, in order to collect further information 
on the proper use of the said drugs and information particularly on safety after marketing, the Ministry of Health, 
Labour and Welfare (MHLW) has instructed to investigate and report the clinical course of patients treated with the 
said drugs, and thus the HRD joint survey has been undertaken jointly by companies having drugs for the treatment 
of HIV infection which are subject to reexamination.
In this survey, patient registration, input of data on survey items, and data verification have been carried out since 
April 2009 using an Electronic Data Capture (EDC) system which is an electronic data collection system on the 
Internet. Please collaborate in this survey.
1. Objectives
This survey is a drug use investigation to investigate the clinical course of patients who received drugs for the 
treatment of HIV infection, which are the reexamination products, understand the occurrence of adverse events under 
actual use conditions and figure out factors affecting safety, in addition to evaluate the therapeutic effectiveness and 
identify factors affecting the effectiveness of the drugs for the treatment of HIV-related diseases.
Survey results will be used as source documents for the reexamination of each drug, and tabulation and analysis 
results will be provided each year to healthcare professionals as feedback for the promotion of the proper use of the 
drugs for the treatment of HIV infection.
2. Target Patients and Target Drugs
The patients of this survey are all patients who are prescribed with drugs for the treatment of HIV infection (see P. 
6) which are subject to reexamination at limited sites.
3. Survey Period
1)  In principle, the drugs for the treatment of HIV infection are designated as orphan drugs, and the reexamination 
period for each drug is 10 years as a rule (see P. 6).
2)  The end date of patient registration for the drug use investigation is as mentioned in page 6.
3)  This survey will enroll patients, who are the continuing patients from clinical trials or clinical trials conducted 
from a humanitarian point of view (expanded access program in Japan), separately after the concerned drugs are 
approved. Also, the survey will enroll patients, who are the continuing patients from post-marketing clinical
trials, separately after the trials of the concerned drugs are completed.
4. Procedures
This survey is a joint survey by companies having drugs for the treatment of HIV infection which are subject to 

3
reexamination (hereinafter referred to as “joint survey participating companies”) and will be outsourced to a 
contracted company [CMIC-PMS Co., Ltd. (hereinafter referred to as “CRO”)].
1)  Request for the survey and a contract
(1) A request and contract for the survey will be, in principle, made between the CRO and a site.
(2) For sites with which contracts have been concluded, the CRO will inform the joint survey participating 
companies that the contracts with the sites have been completed.
2)
Method for data collection
In this survey, patient registration, input of data on survey items, and data verification will be carried out using 
the EDC system. The system to be utilized will be ARCS + PMS (hereinafter referred to as “the System”). 
Security for data transmission will be ensured by authentication of the user’s ID and password assigned to each 
investigator and in accordance with the latest SSL encrypted communication protocol.
3)  Patient registration
(1) After the user’s ID and password are issued for each investigator upon the conclusion of the contract, the 
investigator should enter and send required items (medical record or identification number, patient’s initials [as 
necessary], gender, birth date [age such as age group as necessary], pregnancy status, inpatient/outpatient 
status, name of the target drug and start date of treatment), for patients who have newly started receiving drug 
treatment in or after April of each year or patients who are on drug treatment but have not yet been registered
in the survey on the patient registration screen of the System. It is unnecessary to additionally register patients 
because of drug changes.
(2) The registration numbers of registered patients will be issued by the System.
(3) The continuing patients will be automatically kept registered based on data of the previous-year case report 
forms (CRFs).
4)  Points to consider for data entry, revision, and review
(1) For registered patients, the administration status of each drug by the end of March of each year based on 
medical records and medical charts such as test results and survey results on the clinical course such as 
abnormal changes in laboratory test values and adverse events noted during the survey period should be 
entered and send using the System during period between April and July by the investigator.
(2) When inquiries on data entered were made by the CRO (data clarification request through the System or 
e-mail), the investigator should, as necessary, revise and send the entered data.
(3) When drug treatment is discontinued due to reasons such as a patient’s death or transfer to another hospital, the 
investigator should enter and send the administration status of each drug until discontinuation, the clinical 
course such as abnormal changes in laboratory test values and adverse events, and autopsy status (if the 
outcome is death) using the System.
(4) After completing entry and revision of all investigation items, the investigator should verify the contents of a 
CRF (original) printed out (provided) in (by) the CRO and then sign or affix a seal to the CRF.
5)  Retention of the original CRF
The CRO will collectively retain all CRFs and registration forms.

4
6)  Affixing a signature or seal to the Statement of Confirmation
(1) At the time of signing or affixing a seal to the CRFs, the CRO will prepare and bring the “Statement of 
Confirmation” to the investigator for confirming the survey patients. The Statement of Confirmation is 
intended “to ensure that survey patients are all patients at the site during the survey period”. The investigator 
should verify the Statement of Confirmation and then sign or affix his/her seal to it.
(2) The CRO will retain the original of the signed or sealed “Statement of Confirmation”, prepare the “Statement 
of Confirmation” for each drug based on those from all investigators, and send it to the applicable company.
7)  Notifying adverse drug reactions (ADRs), etc.
(1) When ADRs, etc. (including those for which the causal relationship is unknown) suspected to be associated 
with drugs occurred, the investigator should immediately notify them to the CRO or enter required items in the 
“HRD Joint Survey - Spontaneous Report of ADRs, etc.” form, which is provided beforehand, and fax it to the 
CRO.
When there are two or more companies of which drugs are related to ADRs, etc., the CRO will inform the 
relevant companies.
(2) When the onset of ADRs, etc. is notified, the investigator should collaborate with the CRO that it will, as 
necessary, visit the investigator to collect a detailed report form for ADRs, etc. in the concerned patient, or the 
investigator will enter and send information using the System.
5. Survey Items
1) Common items (CRF for the drug use investigation)
(1) Background
(2) Prescribed anti-HIV drug
(3) Prescribed concomitant medications (including drugs for the treatment of HIV-related diseases)
(4) Concomitant therapies
(5) Patient’s outcome (at the discontinuation of the survey)
(6) HIV-RNA, CD4, Centers for Disease Control and Prevention (CDC) classification, changes over time in body 
weight, and HIV tropism
(7) Abnormal changes in laboratory test values
(8) Adverse events (including ADRs, abnormal changes in laboratory test values, and newly developed 
opportunistic infection)
(9) Relationship with the disease or drug (mandatory for the target drugs administered at the time of onset of the 
adverse event)
(10) Autopsy status (if the outcome is death)
2)  Survey items by product (Separated CRF for Mycobutin Capsules)
(1) MAC infection, etc. (when Mycobutin Capsules is used for tuberculosis, non-tuberculous Mycobacterium
infection including Mycobacterium avium complex (MAC) infection, and prevention of the development of 
disseminated MAC infection in patients with HIV infection)

5
(2) Samtirel (atovaquone) (when Samtirel Oral Suspension 15% is utilized for treatment or prevention of 
development of Pneumocystis pneumonia)
(3) Edurant Tablets (rilpivirine hydrochloride) (when Edurant Tablets are used)
   Complera Combination Tablets (rilpivirine hydrochloride/tenofovir disoproxil fumarate/emtricitabine) (when 
Complera Combination Tablets are utilized)
Record measurement results and other relevant data if blood drug concentrations are measured.
(4) Tivicay Tablets (dolutegravir sodium) and Triumeq Combination Tablets (dolutegravir sodium/abacavir 
sulfate/lamivudine) (when Tivicay Tablets or Triumeq Combination Tablets are used)
(i) Record measurement results and other relevant data if blood drug concentrations are measured.
(ii)When pilsicainide is concomitantly used, separately provide electrocardiographic data.
(iii) Record measurement results if a liver function test (e.g., alanine aminotransferase [ALT], aspartate 
aminotransferase [AST], alkaline phosphatase [AL-P], and total bilirubin [T-Bil]) is performed.
(iv) Record measurement results if a renal function test (e.g., serum creatinine, urine protein, urinary albumin,
and tubular damage markers) is carried out.
(v)Record anti-HIV therapy during 6 months prior to the start of treatment (for patients switching from another 
drug).
(vi) Separately provide test results if gene testing for drug resistance is implemented.
6. Others
1)  Prior to utilizing drugs for the treatment of HIV infection, the investigator should fully explain the details of 
ADRs and other relevant matters to patients, confirm their consent for the treatment and record in their medical 
records that consent has been obtained. When giving the explanation to the patients, the “Information to be 
explained to patients,” which is separately prepared by each of the joint survey participating companies, should 
be used as reference.
2)  Of information on ADRs reported to the MHLW, the patient’s gender, age (age group), primary disease, 
suspected drug, route of administration, ADR term, outcome, suspected concomitant medication(s) and other 
relevant matters will be presented in lists on the “Drug and Medical Device Information Provision,” the website 
of the Pharmaceuticals and Medical Devices Agency (PMDA) via the Internet. Provided information, which 
concerns the patients’ privacy or reporters, will not be reported to the MHLW.
3)  As part of information provision to healthcare professionals, of ADR information notified through the CRF or
“Spontaneous Report of ADRs, etc.” form, the patient’s gender, age (age group), primary disease, complications, 
ADR term, and outcome will be presented on the HRD website (http://www.hrd.gr.jp). Also the results of 
effectiveness and safety tabulations and analyses in the survey will be disclosed through an annual report and 
other means for the “proper use,” “ensuring safety” and “ensuring transparency.” In any event, no provided 
information, which concerns the patients’ privacy or reporters, will be disclosed.

6
7. Where to contact (Inquiries on the contents of the contract, protocol and CRF, registration, collection of the CRF,
and data clarification)
CRO
Contact information
CMIC-PMS Co., Ltd.
1-1-1 Shibaura, Minato-ku, Tokyo
Tel: 0120-204393
Fax: 0120-204292
8. List of Contracted Joint Survey Companies (including distributing companies)
Joint survey participating companies (random 
order)
Contact information
Safety Management Department
ViiV Healthcare K.K.
GSK Building, 4-6-15 Sendagaya, Shibuya-ku, Tokyo
Tel: 03-5786-5202
Fax: 0120-668-322
Safety Measure Promotion Department
MSD K.K.
Urban Ace Kitahama Building 2-3-7 Hiranomachi,
Chuo-ku, Osaka
Tel: 06-6201-1740  Fax: 06-6201-1980
PMS Department
GlaxoSmithKline K.K.
GSK Building, 4-6-15 Sendagaya, Shibuya-ku, Tokyo
Tel: 03-5786-5170  Fax: 03-5786-5219
Drug Information Department
Japan Tobacco Inc.
JT Building 2-2-1 Toranomon, Minato-ku, Tokyo
Tel: 03-5572-4544  Fax: 03-5572-1450
Safety Information Management Department
Torii Pharmaceutical Co., Ltd.
3-4-1 Nihonbashi-Honcho, Chuo-ku, Tokyo
Tel: 0120-40-6839  Fax: 03-5203-7356
Post marketing Study Strategy and 
Management ,Development Japan
Pfizer Japan Inc.
Shinjuku Bunka Quint Building 3-22-7, Yoyogi,
Shibuya-ku, Tokyo
Tel: 03-5309-6820  Fax: 03-5309-9186
PMS Department, Research and Development 
Division
Janssen Pharmaceutical K.K.
3-5-2 Nishikanda, Chiyoda-ku, Tokyo
Tel: 03-4411-5017  Fax: 03-4411-5530
EOD

7
Drugs for the treatment of HIV infection participating in the HRD joint survey
(Marketed drugs which are subject to reexamination as of November 2015)
Anti-HIV drugs
Brand name
Name of drug (abbreviation)
Reexamination period
End 
date 
of 
registration
Prezista Tablets 300 mg
Prezista Tablets 600 mg
Darunavir (DRV)
Darunavir (DRV)
November 2007 to November 2017
December 2014 to November 2017
March 31, 2016
March 31, 2016
Prezista Naïve Tablets 400 mg
Darunavir (DRV)
August 2009 to November 2017
March 31, 2016
Prezista Naïve 800 mg
Darunavir (DRV)
Jul 2013 to November 2017
March 31, 2016
Isentress Tablets 400 mg
Raltegravir (RAL)
June 2008 to June 2018
March 31, 2017
Intelence Tablets 100 mg
Etravirine (ETR)
December 2008 to December 2018 March 31, 2017
Celsentri Tablets 150 mg
Maraviroc (MVC)
December 2008 to December 2018 March 31, 2017
Edurant Tablets 25 mg
Rilpivirine (RPV)
May 2012 to May 2022
March 31, 2021
Complera Combination Tablets
Rilpivirine/tenofovir disoproxil 
fumarate/emtricitabine 
(RPV/TDF/FTC)
November 2014 to May 2022
March 31, 2021
Stribild Combination Tablets
Elvitegravir/cobicistat/emtricitabine/ 
tenofovir disoproxil fumarate 
(EVG/COBI/FTC/TDF)
March 2013 to March 2023
March 31, 2021
Tivicay Tablets 50 mg
Dolutegravir sodium (DTG)
March 2014 to March 2024
March 31, 2022
Triumeq Combination Tablets
Dolutegravir sodium/abacavir 
sulfate/lamivudine (DTG/ABC/3TC)
March 2015 to March 2024
March 31, 2022
Drugs for the treatment of HIV-related diseases
Brand name
Name of drug
Reexamination period
End 
date 
of
registration
Mycobutin Capsules 150 mg
Rifabutin
(Prevention of disseminated 
MAC infection)
July 2008 to July 2018
March 31, 2017
(Tuberculosis, non-tuberculous 
mycobacterium infection)
July 2008 to July 2016
March 31, 2015
Samtirel Oral Suspension 15%
Atovaquone
January 2012 to January 2020
March 31, 2018
If companies other than those having the above drugs wish to take part in this joint drug use investigation, they may 
participate in it while the investigation is ongoing as long as new participating companies comply with verification 
items among the current participating companies.

8
Procedures for Implementation of the HRD Joint Survey
Medical institutions (Sites)
CRO
Participating companies
[CMIC-PMS Co., Ltd.]
<Request and contract>
Issuance of the initial password after concluding the contract
<Patient registration >
<Collection of CRFs>
April of 
each year
<Data clarification>
Site
CRO
PMS 
Department
Request
Informing the conclusion of 
the contract
Acceptance/ contract
[Preparation of the contract status chart per site]
Input and transmission of the CRF
Signing/affixing a seal to the CRF 
(original) and Case Confirmation
Request for completing the CRF 
and case confirmation
Sending a copy of CRF
Input and transmission of registration 
information
Issuance of a registration No.
Fax: 0120-204292
Tel: 0120-204393
Sending a management list 
[Retention of the Case Confirmation (original)]
Sending a copy of Case 
Confirmation
Investigator
EDC system
PMS 
Department
Investi
gator
CRO and
EDC system
PMS 
Department
Request for data clarification
Sending a copy of clarified 
details original (each 
company’s original)
[Summary of reinvestigation items]
Informing clarification items
[Retention of the CRF (original)]
Input and transmission of the 
clarified details
Investigator
CRO and
EDC system
PMS 
Department

9
Procedures for Notifying ADRs, etc.
Medical 
institutions
(Sites)
CRO
Relevant companies 
having suspected 
drugs
[CMIC-PMS Co., Ltd.]
Investigator
Notifying an ADR, etc. by faxing the 
“HRD Joint Survey - Spontaneous 
Report of ADRs, etc.” form
CRO
and
EDC system
PMS
Department
or directly calling
Notification to a relevant company
Request to complete the CRF Note 1)
Notification to a relevant company
Input and transmission using the EDC 
system
Request for data clarification as 
necessary
Request for data clarification as 
necessary
Input and transmission of the clarified 
details
Notification to a relevant company
Request to complete the detailed report 
form at the onset of ADR, etc. Note 2)
Collection of the detailed report form
Request 
for 
a 
detailed 
investigation at the onset of ADR, 
etc. as necessary
Notification to a relevant company
Note 1) EDC system for the CRF for the HRD joint survey
Note 2) Detailed report form for ADRs, etc. in the HRD joint survey
Document No. HIVPMS02 Revision No. 048-A (revised in November 2015)
Fax: 0120-204292
Tel: 0120-204393