CTRI/2022/11/047561 [Registered on: 23/11/2022] Trial Registered Prospectively
Last Modified On:
13/04/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
A phase-I, open label, dose-escalation, safety, tolerability and
pharmacokinetics study of Nor-ursodeoxycholic acid tablets 500 mg
Scientific Title of Study
An open label, phase-I, dose-escalation study to determine safety,
tolerability and pharmacokinetics of Nor-ursodeoxycholic acid tablets
(500 mg, 1000 mg, 1500 mg) in healthy adult human subjects.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
C1B01758, Version #02, Dated 23 May, 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr DHRUV PRAVINKUMAR PATEL
Designation
Principal Investigator
Affiliation
Cliantha Research Limited
Address
Cliantha Research Limited
Cliantha Corporate,
TP 86, FP 28/1,
Off S.P. Ring Road, Sarkhej,
Ahmedabad-382210,
Gujarat, India.
Ahmadabad GUJARAT 382210 India
Phone
9978336240
Fax
Email
dppatel@cliantha.com
Details of Contact Person Scientific Query
Name
Dr DHRUV PRAVINKUMAR PATEL
Designation
Principal Investigator
Affiliation
Cliantha Research Limited
Address
Cliantha Research Limited
Cliantha Corporate,
TP 86, FP 28/1,
Off S.P. Ring Road, Sarkhej,
Ahmedabad-382210,
Gujarat, India.
Ahmadabad GUJARAT 382210 India
Phone
9978336240
Fax
Email
dppatel@cliantha.com
Details of Contact Person Public Query
Name
P Veerendra Kumar
Designation
Head – Clinical Affairs Division
Affiliation
Shilpa Medicare Limited
Address
Shilpa Medicare Limited Unit VII- IDA- Mallapur- Nacharam
Hyderabad
TELANGANA
500076
India
Cliantha Corporate,
TP 86, FP 28/1,
Off S.P. Ring Road, Sarkhej,
Ahmedabad-382210,
Gujarat, India Ahmadabad GUJARAT
9978336240
dppatel@cliantha.com
Details of Ethics Committee
No of Ethics Committees= 1
Name of Committee
Approval Status
Riddhi Medical Nursing Home IEC
Approved
Regulatory Clearance Status from DCGI
Status
Notified
Health Condition / Problems Studied
Health Type
Condition
Healthy Human Volunteers
Healthy Human Volunteers
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Nil
Nil
Intervention
Nor-ursodeoxycholic acid tablets 500 mg
Study will be conducted in 3 cohorts. Subjects will receive Single dose of 500 mg in Cohort-I, Single dose of 1000 mg in cohort-II and Single dose of 1500 mg in cohort-III. Subjects will receive Nor-ursodeoxycholic acid tablets administered orally in a sitting posture with about 240 mL of water at ambient temperature under the supervision of
trained study personnel.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
45.00 Year(s)
Gender
Both
Details
1) Age: 18 to 45 years old, both inclusive.
2) Gender: Male and/or non-pregnant, non-lactating female.
A. Female of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test performed within 28 days
prior to dosing day. They must be using an acceptable form of contraception.
B. For female of childbearing potential, acceptable forms of contraception include the following:
i. Non hormonal intrauterine device in place for at least 3 months prior to the start of the study and remaining in place during the study period, or
ii. Barrier methods containing or used in conjunction with a spermicidal agent, or
iii. Surgical sterilization or
iv. Practicing sexual abstinence throughout the course of the study.
C. Female will not be considered of childbearing potential if one of the following is reported and documented on the medical history:
i. Postmenopausal with spontaneous amenorrhea for at least one year, or
ii. Bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or
iii. Total hysterectomy and an absence of bleeding for at least 3 months.
3) BMI: 18.5 to 30.0 kg/m2, both inclusive; BMI value should be rounded off to one significant digit after decimal point (e.g. 30.04 rounds down to 30.0, while 18.45 rounds up to 18.5).
4) Able to communicate effectively with study personnel.
5) Willing to provide written informed consent to participate in the study.
6) All volunteers must be judged by the principal or sub-investigator or physician as normal and healthy during a pre-study safety assessment performed within 28 days of study medication which will include:
a) A physical examination (clinical examination) with no clinically significant finding.
b) Results within normal limits or clinically non-significant for the following tests:
Hematology - Hemoglobin, Total RBC count, Total WBC count, Platelet count, Differential leukocyte count and HCT
Biochemistry - BUN, Serum creatinine, Random glucose, SGPT & SGOT, Alkaline phosphatase, Uric acid, Serum bilirubin, Total proteins, Albumin & Serum electrolytes
Urinalysis - Color, quantity, specific gravity, odour, appearance, reaction, albumin, bilirubin,
ketone bodies, sugar, urobilinogen and microscopical examination (performed based
on clinical judgment)
Immunological Tests - HIV-I & II, HbsAg, Syphilis (RPR), Anti HCV & Serum (β-HCG) pregnancy test (for female of child bearing potential)
- Additional tests and/or examinations (apart from mentioned in protocol) may be performed, if necessary, based on principal investigator discretion.
- All results will be assessed against the current laboratory normal ranges at the time of testing and a copy of the normal ranges used will be included in the study documentation.
ExclusionCriteria
Details
1) History of allergic responses to Nor-ursodeoxycholic acid, ursodeoxycholic acid or
other related drugs, or any of its formulation ingredients.
2) Have significant diseases or clinically significant abnormal findings during screening
[medical history, physical examination (clinical examination), laboratory evaluations, abdominal ultrasonography recordings, ECG, chest X-ray recording, gynecological history and examination (including pelvic examination and routine breast examination) (for female volunteers)].
3) Any disease or condition like diabetes, psychosis or others, which might compromise
the haemopoietic, gastrointestinal, renal, hepatic, cardiovascular, respiratory, central
nervous system or any other body system.
4) History or presence of bronchial asthma.
5) Use of any hormone replacement therapy within 3 months prior to the dose of study medication.
6) A depot injection or implant of any drug within 3 months prior to the dose of study medication.
7) Use of CYP enzyme inhibitors or inducers within 30 days prior to the dose of study medication.
8) History or evidence of drug dependence or of alcoholism or of moderate alcohol use.
9) Smokers who smoke 10 or more cigarettes per day or 20 or more biddies per day or those who cannot refrain from smoking during the study period.
10) History of difficulty with donating blood or difficulty in accessibility of veins.
11) A positive hepatitis screen (includes subtypes B & C).
12) A positive test result for HIV antibody and / or syphilis (RPR).
13) Volunteers who have received a known investigational drug within seven elimination
half-life of the administered drug prior to the housing.
14) Volunteers who have donated blood or loss of blood 50 ml to 100 ml within 30 days or 101 ml to 200 ml within 60 days or >200 ml within 90 days (excluding volume drawn at screening for this study) prior to dosing of study medication, whichever is greater.
15) History of difficulty in swallowing or of any gastrointestinal disease, which could affect drug absorption.
16) Intolerance to venipuncture
17) Any food allergy, intolerance, restriction or special diet that, in the opinion of the principal investigator or sub-investigator, could contraindicate the volunteer’s participation in this study.
18) Institutionalized volunteers.
19) Use of any prescribed medications within 14 days prior to housing.
20) Use of any OTC products, vitamin and herbal products, etc., within 7 days prior to housing.
21) Use of grapefruit and grapefruit containing products within 7 days prior to housing.
22) Ingestion of any caffeine or xanthine products (i.e. coffee, tea, chocolate, and caffeine containing sodas, colas, etc.), cigarettes and tobacco containing products, recreational drugs, alcohol or other alcohol containing products within 96 hours prior to housing.
23) Ingestion of any unusual diet, for whatever reason (e.g.: low sodium) for three weeks prior to housing.
Method of Generating Random Sequence
Other
Method of Concealment
An Open list of random numbers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Incidence of study drug-related DLTs (Safety) and assessment of tolerability after single dose administration at dose levels of 500mg and 1000mg and 1500 mg
A total of 34 venous blood samples will be collected in each Cohort.
Blood samples will be collected at -48.0, -42.0, -36.0, -30.0, -24.0, -18.0,
-12.0, -6.0, pre-dose (0.0) hours prior to dosing and at 0.083 (5 minute),
0.167 (10 minute), 0.333 (20 minute), 0.5 (30 minute), 0.667, 0.833, 1.0,
1.167, 1.334, 1.5, 1.667, 1.834, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0,
24.0, 36.0, 48.0 and 72.0 hours post dose.
Secondary Outcome
Outcome
TimePoints
Pharmacokinetic parameters will be calculated on below
1. Pharmacokinetic parameters at dose level
2. Primary Pharmacokinetic parameters at each dose level
Cmax, AUC0-t and AUC0-inf
3. Secondary Pharmacokinetic parameters at each dose level
Tmax, Kel, AUC%extrapolation, CL, Vd and t1/2
4. Dose proportionality
A total of 34 venous blood samples will be collected in each Cohort.
Blood samples will be collected at -48.0, -42.0, -36.0, -30.0, -24.0, -18.0,
-12.0, -6.0, pre-dose (0.0) hours prior to dosing and at 0.083 (5 minute),
0.167 (10 minute), 0.333 (20 minute), 0.5 (30 minute), 0.667, 0.833, 1.0,
1.167, 1.334, 1.5, 1.667, 1.834, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0,
24.0, 36.0, 48.0 and 72.0 hours post dose.
Target Sample Size
Total Sample Size="42" Sample Size from India="42" Final Enrollment numbers achieved (Total)= "42" Final Enrollment numbers achieved (India)="42"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a phase-I open label, dose-escalation, safety, tolerability and
pharmacokinetics study.
Study Objectives:
01. To evaluate safety and tolerability of single ascending doses of Nor-ursodeoxycholic
acid tablets (500 mg, 1000 mg & 1500 mg) in healthy adult human subjects.
02. To determine the pharmacokinetics of Nor-ursodeoxycholic after single dose oral
administration.
Dose proportionality:
Dose proportionality, after single dose oral administration Nor-ursodeoxycholic acid tablets at 500 mg to 1500 mg