| CTRI Number |
CTRI/2022/03/041166 [Registered on: 17/03/2022] Trial Registered Prospectively |
| Last Modified On: |
16/03/2022 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
|
Type of Study
|
|
| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
To evaluate bioavailability study of curcumin micro emulsion soft gel Capsules 500 mg with Curcumin c3 complex® 500 mg capsules in healthy, adult human subjects under Fasting conditions. |
|
Scientific Title of Study
|
AN OPEN LABEL, BALANCED, RANDOMIZED, SINGLE-DOSE, TWO-TREATMENT, TWO-SEQUENCE, TWO-PERIOD, TWO-WAY CROSSOVER ORAL BIOAVAILABILITY STUDY OF CURCUMIN MICRO EMULSION SOFT GEL CAPSULES 500 MG MANUFACTURED FOR AMITOJAS PVT LTD AND MANUFACTURED BY GELTEC PVT LTD, INDIA WITH CURCUMIN C3 COMPLEX® 500 MG CAPSULES MANUFACTURED BY DOCTORS BEST. INC, USA, IN HEALTHY, ADULT HUMAN SUBJECTS UNDER FASTING CONDITIONS. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| ; BIAG-CSP-054 & SLS-CT-0002-22-VIT, D:25-Jan-2022, V: 1.0 |
Protocol Number |
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|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Annamalai |
| Designation |
Principal Investigator |
| Affiliation |
Spinos Lifescience and Research Pvt Ltd. |
| Address |
29 A Krishna Maduravanam, Vellakinar Pirivu, G.N. Mills Post, Coimbatore-641029
Coimbatore
TAMIL NADU
641029
India |
| Phone |
04222642491 |
| Fax |
|
| Email |
annamalai.k@spinoslifescience.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Divya C |
| Designation |
CEO |
| Affiliation |
Bioagile Therapeutics Pvt Ltd |
| Address |
#2/5, Dahlia Building, 3rd Floor, 80 Feet Road, RMV 2nd Stage, Dollars Colony Bangalore 560094
Bangalore
KARNATAKA
560094
India |
| Phone |
9538961761 |
| Fax |
|
| Email |
Divya@bioagiletherapeutics.com |
|
Details of Contact Person
Public Query
|
| Name |
Divya C |
| Designation |
CEO |
| Affiliation |
Bioagile Therapeutics Pvt Ltd |
| Address |
#2/5, Dahlia Building, 3rd Floor, 80 Feet Road, RMV 2nd Stage, Dollars Colony Bangalore 560094
Bangalore
KARNATAKA
560094
India |
| Phone |
9538961761 |
| Fax |
|
| Email |
Divya@bioagiletherapeutics.com |
|
|
Source of Monetary or Material Support
|
| Spinos Lifescience and Research Pvt Ltd
No.29 A, “Krishna Madhuravanamâ€,
Vellakinar Pirivu, Thudiyalur, Coimbatore-641029.
Tamil Nadu, India.
|
|
|
Primary Sponsor
|
| Name |
Amitojas Wellness Pvt Ltd |
| Address |
#3-100-55/739, Block-A, 2nd Floor, JK Arcade Jayaberi Park, Kompally, Hyderabad, Telangana – 500014 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
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Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Annamalai |
Spinos Lifescience and Research Pvt Ltd |
Spinos Lifescience and Research Pvt Ltd 29 A Krishna Maduravanam, Vellakinar Pirivu, G.N. Mills Post, Coimbatore-641029
Coimbatore
TAMIL NADU |
8637620087
annamalai.k@spinoslifescience.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Research Ethics Committee |
Approved |
|
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Regulatory Clearance Status from DCGI
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Healthy Human Volunteers |
ADULT HUMAN SUBJECTS UNDER FASTING CONDITIONS |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Curcumin C3 Complex® |
Curcumin C3 Complex®500 mg Capsules in period 1 and 500mg in period 2 by oral administration in duration of 12 days. |
| Intervention |
Curcumin Micro emulsion |
Micro emulsion soft gel capsules 500 mg in period 1 and 500mg in period 2 by oral administration in duration of 12 days. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
45.00 Year(s) |
| Gender |
Both |
| Details |
1.Normal, healthy, adult, human subjects of age between 18-45 years with a Body
Mass Index (BMI) ranges between 18.50 kg/m2 to 29.99 kg/m2 (according to the
formula of BMI weight (kg) or[height (m)]2)
2.Subjects who have no evidence of underlying disease during screening and check-in
and whose screening is performed within 21 days of check in.
3.Subjects whose screening laboratory values are within normal limits or considered
by the physician or principal or clinical investigator to be of no clinical significance.
4.Healthy as documented by the medical history, physical examination (including but
may not be limited to an evaluation of the cardiovascular, gastrointestinal,
respiratory, musculoskeletal and central nervous systems) and vital sign
assessments.
5.Generally healthy as documented by 12-lead electrocardiogram (ECG), X-Ray and
clinical laboratory assessments.
6.Non- smokers or ex-smokers are defined as someone who has completely stopped
smoking for at least the past 03 months.
7.Willing to consume Ovo lacto vegetarian diet.
8.Willing to comply with all requirements of this study protocol as well as instructed
by the study personnel.
9.Generally healthy as documented by gynecological examination and breast
examination (for female subjects – period I only).
10.Female subjects within normal limits or clinically non-significant laboratory
evaluation results for FSH.
11.Females of childbearing potential must have a negative serum pregnancy test
performed within 21 days prior to initiation of the study and a negative urine
pregnancy test prior to check-in of each period.
12.If subject is female; currently not pregnant, not lactating, or not attempting to
become pregnant for 4 weeks before the screening visit, throughout the duration of
the study and 3 weeks after the subject’s last study-related visit (for eligible subjects
only, if applicable), has a negative pregnancy test, and is of
non-childbearing potential, defined as:
1 year post-menopausal (no menstrual period for at least 12 consecutive
months without any other medical cause)
Surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or
hysterectomy)
or is of
childbearing potential, willing to commit to using a consistent and acceptable
method of birth control as defined below for the duration of the study:
double barrier methods (condoms, cervical cap, diaphragm, and vaginal
contraceptive film with spermicide)
intrauterine device (IUD) with a low failure rate less than 1 percent per year
or is of
childbearing potential and not sexually active, willing to commit to using a
consistent and acceptable method of birth control as defined above for the
duration of the study, in the event the subject becomes sexually active.
13.If male and sexually active, the subject is willing to commit to 2 acceptable methods
of birth control for the duration of the study.
14.The subject and their partners are willing to use 2 types of contraception, one of
which is a barrier method, such as the use of a condom throughout the study.
|
|
| ExclusionCriteria |
| Details |
1.Evidence of allergy or known hypersensitivity to Curcumin or its inactive ingredients.
2.Subjects with hepatic encephalopathy, cholestasis, myasthenia, pre-existing liver
disease, alcohol abuse, existing tinnitus and pre-existing gallbladder disease. Any
major illness in the last three months or any significant ongoing chronic medical
illness.
3.Renal or liver impairment.
4.Any disease or condition which might compromise the hemopoeitic, gastrointestinal,
renal, hepatic, cardiovascular, Musculoskeletal, respiratory, central nervous system,
diabetes, psychosis or any other body system.
5.History of alcohol addiction or abuse.
6.Consumption of caffeine and /or Xanthine containing products (i.e. coffee, tea,
chocolate, and caffeine-containing sodas, colas, etc.) tobacco containing products for
at least 48.00 hours prior to check-in and throughout the entire study.
7.Consumption of alcohol and its products, grapefruit and/ or its juice and poppy
containing foods within 72.00 hours prior to check-in and throughout the entire study.
8.Subjects who have taken any prescription medications within 14 days prior to study
check-in and throughout the study and any over the counter medicinal products,
herbal medications within 07 days prior to check-in and throughout the study.
9.Subjects who have taken an unusual diet, for whatever reason (e.g. low salt) for 48.00
hours prior to check-in and throughout the study.
10.Subject who had participated in any other study within the 90 days of check-in.
11.History of difficulty in swallowing.
12.History of difficulty in accessibility of veins.
13.Positive results for urine screen of drugs of abuse (Marijuana-THC, amphetamineAMP, barbiturates-BAR, cocaine-COC, benzodiazepines-BZD and morphine-MOR)
in urine prior to check-in of each period.
14.Positive results for alcohol test prior to check-in of each period.
15.Any blood donation / excess blood loss within 90 days of check-in.
16.Ingestion of any hormonal agent at any time within 14 days prior to start of study
check-in.
17.Use of hormone replacement therapy for a Period of 06 months prior to dosing.
18.Female subjects demonstrating a positive pregnancy screen.
19.Female subjects who are currently lactating.
20.Females likely to become pregnant during conducting of the study. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
To determine the oral Bioavailability of Curcumin micro emulsion soft gel
capsules 500 mg Manufactured by Geltec Pvt Ltd, India with Curcumin C3
complex® 500 mg Capsules, Manufactured by Doctors best. Inc, USA, in
healthy, adult, human subjects under fasting conditions. |
12 days of period |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To monitor the safety and tolerability of a single dose administered in
healthy human adult subjects under fasting conditions.
|
48 hours |
|
|
Target Sample Size
|
Total Sample Size="36"
Sample Size from India="36"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
21/03/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="0"
Months="1"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
The curcumin exhibits poor bioavailability is well documented. The major reasons attributed to
the low bioavailability of curcumin are poor absorption, rapid metabolism, and rapid systemic
elimination. In humans a comprehensive pharmacokinetic data do not exist. The pilot studies summarized that low systemic bioavailability is observed in humans following oral dosing. First
phase I clinical trial of curcumin was done in 25 patients with high-risk or pre-malignant lesions.
The starting dose was 500 mg/day and if no toxicity was noted, the dose was then escalated to
another level in the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. There was no
treatment-related toxicity up to 8 g/day but the bulky volume of the drug was unacceptable to the
patients beyond 8 g/day. The serum concentration of curcumin usually peaked at 1 to 2 hours
after oral intake of curcumin and gradually declined within 12 hours. The average peak serum
concentrations after taking 4,000 mg, 6,000 mg and 8,000 mg of curcumin were 0.51 +/− 0.11
μM, 0.63 +/− 0.06 μM and 1.77 +/− 1.87 μM, respectively. Urinary excretion of curcumin was
undetectable. Lao et al conducted a pilot study in 24 healthy subjects and they administered
curcumin up to 12g/day. They detected curcumin in the serum samples of only those who took
10 and 12g/day. It was reported that a daily oral dose of 3.6g of curcumin results in detectable
levels in colorectal tissue, which might be sufficient to exert pharmacological activity. Curcumin
undergoes metabolism in the liver particularly via glucuronidation and sulfation. The metabolites
of curcumin such as glucoronides appear to lack any pharmacological activity.
The systemic elimination of curcumin is another contributing factor for low bioavailability of
curcumin. The initial reports by Wahl storm and Blennow showed that after oral administration
of 1g/kg curcumin to rats, more than 75% of curcumin was excreted in feces and negligible
amount was detected in urine
Increase the bioavailability of curcumin, is also being explored. The roles of adjuvant, which can
block the metabolism of curcumin, are of great interest. Combining curcumin with Piperine has
been shown to increase the bioavailability in rats and in human subjects. Piperine is an inhibitor
of glucuronidation of curcumin. The study conducted by Shobha et al demonstrated that
concomitant administration of curcumin with Piperine produced 150% increase in bioavailability
in rats and 2000% increase in man. Other ways to improve the bioavailability of curcumin is by
making curcumin nanoparticles micelles and phospholipid complexes.
The possible advantages attributed to such formulations are
(a) Provide longer circulation
(b) Increase the cellular permeability and (c) Induce resistance to metabolic processes.
Systemic elimination or clearance of curcumin from the body is an important factor determining
its biological activity. Wahlstorm and Blennow reported that, when 1 g/kg curcumin was given
orally to rats, 75% was excreted in the feces and negligible amounts were found in the urine. A
clinical study of 15 patients receiving oral curcumin in doses between 36 and 180 mg daily for
up to 4 months found neither curcumin nor its metabolites in urine, but the drug was recovered
from feces. The absorption and elimination half-life of orally administered curcumin (2 g/kg) in
rats were reported to be 0.31 0.07 and 1.7 0.5 h, respectively. However, the same dose of
curcumin in humans did not allow the calculation of these half-life values because serum
curcumin levels were below detection limits at the majority of time points in most of the
experimental patients. Existing evidence in the literature is insufficient to draw conclusions
about the factors controlling the in vivo elimination half-life of curcumin, and future studies are
warranted to address this issue [7]
. |