SIV Slide deck_Hypertension Study.pptx

PROTOCOL NUMBER: GPL/CT/2022/012/IV
HYPERTENSION STUDY
GPL/CT/2022/012/IV
Presented By : CRA Name

Study Title
Protocol Title: A Prospective, Open label, Randomized, Multicenter, Post marketing study comparing
Effectiveness and Safety of Telmisartan plus Amlodipine with Telmisartan plus Cilnidipine in subjects with
Hypertension and Renal Impairment
Protocol Number: GPL/CT/2022/012/IV
Version Number: 1.0
Date of Protocol: 12-Oct-2022

Index (1/2)
Sr.No. Contents
1. Study Title
2. Study Details
3. Introduction
4. Study Objective & Endpoints
5. Inclusion Criteria
6. Exclusion Criteria
7. Study Flow
8. Schedule of Events
9. Number of Subject
10. Investigational Products
11. Lab Investigations

Index (2/2)
Sr.No. Contents
12. Concomitant Medications
13. Subject Withdrawal from Study
14. Study Timelines and Enrollment Expectations
15. EDC Overview, Account set-up & Training
16. Monitoring Expectation & Site Monitoring
17. Adverse Event and Serious Adverse Event
18. Data Management
19. Data Analysis
20. Audit
21. Inspection
22. Record Retention
23. Site List

Study Details
Name of Sponsor Glenmark Pharmaceuticals Ltd.
Name of Investigational Product,
dosage and route of administration
FDC of Telmisartan 40/80 mg and Amlodipine 5mg Oral Once Daily,
FDC of Telmisartan 40/80 mg + Cilnidipine 10 mg Oral Once Daily
Dosage- 1 tablet to be taken once daily, orally with plain water after meal, daily
for 365 days
Indication Hypertension and Renal impairment
Protocol Version & Date 1.0 & 12-Oct-2022
Study Centers 06
Study Phase PMS
Randomization The eligible patients would be randomized in ratio of 1:1 using computer
generated randomization to receive either of two treatment groups.
Number of subject to be enrolled 188 Subjects
94 Subjects per treatment group

Introduction
Hypertension (HTN) is a public health menace contributing up to 45% of cardiovascular diseases (CVD) deaths
and 51% of stroke deaths. In India up to 33% of urban and 25% of the rural population are afflicted with the
disease.
Attainment of blood pressure (BP) goals in the population at large is a major challenge and area of focus of
health systems worldwide. Over the years, BP targets have been continuously redefined as the armamentarium of
drugs has expanded
Cilnidipine and Telmisartan is a combination of medicines used to lower the blood pressure more effectively,
thereby lowering the chances of having a stroke or heart attack.
Telmisartan and Amlodipine is a combination of medicines that may be used alone or with other medicines to
treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it
continues for a long time, the heart and arteries may not function properly.
Renin-angiotensin system (RAS) inhibitors are beneficial as first-line antihypertensive agents for hypertension and
renal impairment in patients with or without diabetes. Calcium channel blockers (CCBs) are frequently added in
these patients if RAS inhibitors are not able maintain the BP below 130/80 mmHg which is the recommended
goal BP in patients with hypertension and renal impairment

Study Objectives & Endpoints(1/3)
Study Objectives
1. Primary Objective
To evaluate and compare the effect of Telmisartan plus Amlodipine Vs. Telmisartan plus Cilnidipine on renal
parameters and blood pressure in subjects with hypertension and renal impairment.
2. Secondary Objective
To evaluate and compare the safety of Telmisartan plus Amlodipine Vs. Telmisartan plus Cilnidipine in subjects
with hypertension and renal impairment.

Study Endpoints
1. Primary Endpoint
To evaluate and compare the effect of Telmisartan plus Amlodipine Vs. Telmisartan plus Cilnidipine on renal
parameters and blood pressure in subjects for hypertension with renal impairment by the-
Change from baseline in urinary albumin-creatinine ratio (UACR) at Week 52.
Time Frame: Visit-1, Visit-4 & Visit 6
2. Secondary Endpoint
To evaluate and compare the effect of Telmisartan plus Amlodipine Vs. Telmisartan plus Cilnidipine in subjects
suffering from hypertension and renal impairment by the-
 Change from baseline in estimated glomerular filtration rate (eGFR) at Week 52

Study Endpoints
 Change from baseline in office blood pressure at Week 52
 Change from baseline in serum creatinine levels at Week 52
 Change from baseline in serum uric acid levels at Week 52
To evaluate and compare the safety of Telmisartan plus Amlodipine Vs. Telmisartan plus Cilnidipine in subjects
suffering from hypertension and renal impairment by the-
Incidence of adverse effects of Telmisartan plus Amlodipine Vs. Telmisartan plus Cilnidipine at follow up visits of
treatment
Time Frame: Visit-1, Visit-4 & Visit 6

Inclusion Criteria
1. Male or female subjects aged between 18 to 75 years.
2. Subjects with ability to understand and provide written informed consent form, which must have been
obtained prior to screening.
3. Subjects with hypertension (systolic/diastolic BP ≥ 130/80 and < 180/110 mmHg).
4. Subjects with hypertension and renal impairment (eGFR 60-90 ml/min/1.73m2 and urinary albumin in the
range of 30–600 mg/g creatinine).
5. Subjects with hypertension requiring antihypertensive treatment with two drug therapy.
6. Subjects on stable dose of antihypertensive treatment with Telmisartan for ≥ 3 months before the enrolment.
7. Subjects not on CCB treatment for their hypertension management for ≥3 months before the enrolment.
8. Subjects willing to comply with the protocol requirements.

Exclusion Criteria(1/3)
1. Presence of any clinically relevant disease/disorder (e.g., severe hepatic impairment, chronic renal failure,
thromboembolic disorders, coronary artery or cerebrovascular diseases, uncontrolled diabetes (HbA1c
≥7%), uncontrolled thyroid disorder etc.).
2. Causes of renal disease other than hypertension or T2DM.
3. Urinary tract infections.
4. Acute Kidney Injury (AKI).
5. Subjects of T1DM.
6. Subjects of T2DM diagnosed more than 1 year prior to screening.
7. Severe hypertension (≥180/110 mmHg).
8. Serum creatinine ≥2.0 mg/dL in men or ≥1.5 mg/dL in women.

9. Subjects, in opinion of investigators, requiring initiation of treatment with initial monotherapy.
10. Surgical or medical condition that, in the judgment of the Investigator, could interfere with
absorption, distribution, metabolism, or excretion of the drugs to be used.
11. Presence or history of secondary or malignant hypertension.
12. Any known cardiac disease/disorder in which any of the study medication is contra-indicated.
13. Current or recent substance abuse, including alcohol.
14. Refusal or inability to comply with the requirements of the protocol for any reason, including
scheduled clinic visits and laboratory tests.
15. Participation in any experimental drug study within 60 days before screening.
16. Breast feeding or pregnant females or Females with child-bearing potential who do not follow
adequate contraceptive measures.

17. Concomitant or prior (within 60 days of screening) use of any of the following medications: calcium channel
blocker, clonidine, aliskerin.
18. Subjects having intolerance, hypersensitivity or any other contraindication to any of the Investigational
products.
19. History of HIV, Hepatitis B and Hepatitis C.

Study Flow
Screening-Visit 1(Day -5 to Day 0)
Screen failure
Do not enroll the subject
Subjects fulfilling inclusion/exclusion
criteria will be enrolled in the study
Blood & urine samples will be collected
Baseline /Randomization/ IP Dispensation Visit 2 (Day-1)
Follow up visit Visit 3( Day 90+7days)
Follow up visit Visit 4 (Day 180+7days)
End of Study Visit Visit 6(Day 365 +7days)
Follow up visit Visit 5 (Day 270+7days)

Schedule of Events (1/2)
Study Period Visit-1
Scree
ning
(Day -
5 to 0)
Visit-2
Baseline
(Day 1)
Visit-3
Treatment
Period
(Day 90+
7days)
(3 months)
Visit-4
Treatment
Period
(Day 180+
7days)
(6 months)
Visit-5
Treatment
Period
(Day 270+
7days)
(9 months)
Visit-6
End of Study
Visit
(Day 365 +
7days)
(12 months)
1. Written informed consent X
2. Inclusion / Exclusion criteria X
3. Demographics X
4. Medical and surgical history X
5. Prior and concomitant
medications
X X X X X X
6. Physical examination X X X X X X
7. Height X
8. Weight X X X X X X

Schedule Of Events (2/2)
Study Period Visit-1
Scree
ning
(Day -
5 to 0)
Visit-2
Baseline
(Day 1)
Visit-3
Treatment
Period
(Day 90+
7days)
(3 months)
Visit-4
Treatment
Period
(Day 180+
7days)
(6 months)
Visit-5
Treatment
Period
(Day 270+
7days)
(9 months)
Visit-6
End of Study
Visit
(Day 365 +
7days)
(12 months)
9. Vital signs (BP, body temperature,
heart rate, respiratory rate)
X X X X X X
10. 12-lead ECG X X X
11. Laboratory Investigationsa X X X
12. Urine Pregnancy testb X X
13. Assessment of AEs/SAEs X X X X X X
14. Study Drug Dispensation X X X X
15. Study Drug Return/Compliance X X X X
a- CBC, eGFR, serum uric acid, serum creatinine, Urine Albumin Creatinine Ratio (UACR) & HbA1c
b- To be performed in females of childbearing potential.

Number of Subjects
A total of 188 patients (94 patients in each arm) will be enrolled in this study.
The eligible patients would be randomized in ratio of 1:1 using computer generated randomization to receive
either of two treatment groups

Investigational Products
Investigational products-
A) FDC of Telmisartan 40/80 mg + Amlodipine 5 mg and
B) FDC of Telmisartan 40/80 mg + Cilnidipine 10 mg
Dosage- 1 tablet to be taken daily, orally with plain water daily for 12 months.
Note: Initially 40 mg Telmisartan will be dispensed to the each subject in both group.
As per the PI discretion, 80 mg of Telmisartan will be dispensed to 15-20 % of the subject ,if the subjects do
not respond to 40 mg of Telmisartan.
Treatment No. of subjects Treatment Schedule
Arm I
FDC of Telmisartan 40/80 mg +
Amlodipine 5 mg
94 1 tablet to be taken daily, orally with plain water
after meals daily for 12 months.
Arm II
FDC of Telmisartan 40/80 mg +
Cilnidipine 10 mg
94 1 tablet to be taken daily, orally with plain water
after meals daily for 12 months.

Lab Investigations
Below mentioned Laboratory & other assessments will be performed at Visit 1 (Screening Visit) , Visit 4 (Day
180 _6 months + 7days) and Visit 6 (Day 365 _12 months + 7days )
a. 12-lead ECG
b. CBC
c. Urine Analysis- Urine Albumin Creatinine Ratio (UACR)
d. Biochemistry- e-GFR, Serum Creatinine and Serum Uric Acid
e. HbA1c
f. Urine Pregnancy test (only for females of childbearing potential)
Blood and Urine sampling
Blood sample will be withdrawn at visits to check safety, tolerability and efficacy of Telmisartan plus Amlodipine
Vs. Telmisartan plus Cilnidipine- 5 ml of blood sample & 10 ml of urine will be withdrawn at visits – Visit 1,
Visit-4 and Visit 6.

Concomitant Medications
Excluded Concomitant Medication:
1 Calcium Channel Blocker,
2. Clonidine and
3. Aliskerin.

Subject Withdrawal From Study
A subject may voluntarily withdraw their consent in this study at any time.
The Investigator may also, at his/her discretion, withdraw the subject from participating in this study at any
time, or the sponsor may discontinue the study.
If the subject is withdrawn from participation in the study for any reason, the investigator must make every
effort to perform the efficacy and safety evaluation.
The date of completion or withdrawal and reason for withdrawal will be documented in the subject's CRF.
Reasons for early withdrawal from the study include:
Study closed/terminated
Lost to follow-up
Investigator discretion, with reason to be specified
Withdrew consent

Study Timelines and Enrollment Expectations
Enrollment Target Timelines
Total number of expected enrolled subjects 188
94 Subjects per treatment group
Number of subjects expected to be enrolled at your
site
31
Number of Study Sites 06
Enrollment period 03 months
Total Duration 12 months

EDC Overview, Account set-up & Training(1/2)
Data will be captured & stored in the e-CRF by using Clinsoft™
Clinsoft™ is the -
◦ Internet-based application
◦ No data are processed or stored on the user’s computer
◦ No software download or plug-in needed
◦ Browser Independent

EDC Overview, Account set-up & Training(2/2)
ClinSoft V1.0 is 21 CFR part 11 compliant software that facilitates the process for transforming the paper or
eCRF - based study data into the access control electronic validated query free analyzable data.
eCRF training will be provided to the study staff with the help of demo link.
CRA will provide a user creation form to the site personnel i.e. Principal Investigator, Site CRC.

Monitoring Expectation and Site Monitoring (1/2)
Site monitoring visits will take place depending upon site recruitment.
Total 3-4 monitoring visits will be performed during the subject recruitment period.
The first monitoring visit will be performed within 10 working days of enrolment of the first 5 -10
subjects at the site.
Second monitoring will be performed after enrolment and completion of 15 to 25 subjects at the
site and third monitoring will be performed after enrolment and completion of 31 subjects at each
site
Additional monitoring visit (if required)will be done as per the discussion with PI.

Following activities will be performed during site monitoring visit-
Review IC Forms & Procedure
Availability of Photo ID in respective files with sign and date.
Review of source documents such as medical history, lab reports and prescriptions.
Review of eCRFs
Review-Storage of IMP & Clinical Supplies
IMP Accountability
AE & SAE Review
Review of Investigator’s Site File
Monitoring Expectation and Site Monitoring (2/2)

Adverse Events and Serious Adverse Events
(1/3)
Detection of Adverse Events
The investigator & team is responsible for detecting, assessing, documenting and reporting of all Adverse
Events.
Adverse Events reports should also be solicited by asking subjects how they feel/have felt since the last
visit/examination.
Subjects will also be encouraged to report Adverse Events occurring at any other time during the study.
Reporting Serious Adverse Events
All adverse events will be communicated to the Chairman / Chairperson, Institutional / Independent Ethics
Committee, according to your EC Timeline.

(2/3)
Detection of Serious Adverse Events
Any Adverse Event that fulfills any one of the criteria listed below must be recorded as a Serious Adverse
Event:-
Results in death.
Is life-threatening.
Requires inpatient hospitalization or prolongation of existing hospitalization,
Results in persistent or significant disability/incapacity, or
Is a congenital anomaly/birth defect.
Is an important medical event.

(3/3)
Reporting Serious Adverse Events
All serious adverse events will be communicated to the Chairman / Chairperson, Institutional / Independent
Ethics Committee, Study Director and Sponsor representative.
Detailed information about the serious adverse event(s) shall be reported within 07 working days of occurrence
to Chairman / Chairperson, IEC. Detailed information about the serious adverse event(s) will be sent to the
CRO’s representative and Study Director within 24 hours of their occurrence.
Information will be sent to the following address:
CRO Representative : Dr. Devesh Kumar
Tel : +91- 9971169602
E-mail : devesh.kumar@innovate-research.com
Sponsor Representative:
E-mail: GlobalPV@glenmarkpharma.com

Data Management
Data from the study will be managed by Innovate Research Pvt. Ltd. Data Management for the study will be
done in Clinical Data Management System (CDMS) with the compliance of FDA 21 CFR Part 11 and industry
guidelines. e-CRF will be used to store the data.
All data will be recorded on the source note & data will be captured in the e-CRF.
The Investigator will allow representatives of the sponsor, regulatory agencies, and their designees to inspect
all study documents (including, but not limited to, consent forms, study drug accountability forms, IRB/EC
approvals) and pertinent hospital or clinic records for confirmation of data throughout and after completion
of the study.

Data analysis
DATA ANALYSIS PLAN
Safety endpoints will be analyzed using the safety population, consisting of all Subjects who have taken at least
one dose of the study medication.
Efficacy endpoints will be analyzed using the per-protocol (PP) population as well as the modified intention to
treat (mITT) population (‘mITT may be defined as all subjects who take one dose of medication and have
baseline measures’). For efficacy analyses, the last observation carried forward (LOCF) methodology will be
used when data are missing.
General Approach for Safety Data Analysis
Data on patient disposition (number of Subjects enrolled, number of withdrawals, and reasons for
withdrawal) as well as the number of Subjects included in each population will be appropriately summarized.
Demography (age, sex, height, weight, alcohol and smoking status), and baseline characteristics (medical
history, physical examination, vital signs, and past medical history) will be appropriately summarized.
All SAE / AE (volunteered & observed) will be recorded.

Audit
An audit is a systematic and independent review of trial-related activities and documents to determine
whether trial-related activities were conducted and the data were accurately recorded and analyzed according to
the protocol, SOPs, GCP and the appropriate requirements.
In conducting this study, the Investigator accepts that the sponsor, ethical committee or regulatory body may
at any time by appointment conduct an audit of the study site.

Inspection
An inspection is defined as the act of a regulatory authority of conducting an official review of documents,
facilities, records and any other resources that are deemed by the authorities to be related to the clinical trial
and that may be located at the site of the trial, or at the sponsors or any other establishments deemed
appropriate by the regulatory authorities.

Record Retention
It is the responsibility of the Investigator to retain study essential documents for the minimum period of 3
years or as per current regulations, after completion of the study.
These documents should be retained for a longer period, if required, by an agreement with the Sponsor.
In such an instance, it is the responsibility of the Sponsor to inform the Investigator/institution as to when
these documents no longer need to be retained.

Site List
PI Name Site Name & Address Site Type
Dr. Harsh Mittal Panchsheel Hospital, lock - C3, 64/A, Block C, Yamuna Vihar,
Shahdara, North East, Delhi, 110053
Private
Dr. Chinmoy Barik College of Medicine & J.N.M. Hospital, Department of
Medicine, Kalyani, Nadia, West Bengal-741235
Government
Dr. Chandrashekhar S.
Gillurkar
Gillurkar Multispeciality Hospital, 20, Reshimbag, Umred road,
Sakkardara, Nagpur-9, Maharashtra
Private
Dr. Sandeep Kumar
Gupta
MV Hospital & Research Center , 314/30, Mirza Mandi,
Chowk, Lucknow-226003 Uttar Pradesh, India
Private
Dr. Mukulesh Gupta Udyaan Health Care Pvt. Ltd. ,730, Udayn-1 Eldeco, Near Bangla
Bazar, Lucknow(U.P.) 226012
Private
Dr. Santosh Saklecha Santosh Hospital, /1, Promenade Rd, Near Coles Park,
Frazer Town, Bengaluru, Karnataka-560005
Private

I WOULD NOW BE INTERESTED TO HEAR FROM
YOU WITH YOUR QUESTIONS

Thank you

SIV Slide deck_Hypertension Study.pptx

Recommended

Recommended

More Related Content

Similar to SIV Slide deck_Hypertension Study.pptx

Similar to SIV Slide deck_Hypertension Study.pptx (20)

Recently uploaded

Recently uploaded (20)

SIV Slide deck_Hypertension Study.pptx