| CTRI Number |
CTRI/2022/03/041189 [Registered on: 17/03/2022] Trial Registered Prospectively |
| Last Modified On: |
28/03/2022 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
|
Type of Study
|
|
| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
Comparative Pharmacokinetics study |
|
Scientific Title of Study
|
An Open-label, Randomized, 2-Period, Crossover Study to Assess the Comparative Pharmacokinetics of LSP-5415 and NuvaRing® in Healthy Adult Females |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| CVR-WH-201 Version No. Final, Date 20-OCT-2021 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Yashvant Khaire |
| Designation |
Clinical Investigator |
| Affiliation |
Raptim Research Pvt. Ltd. |
| Address |
Raptim Research Private Limited
A-226, PAP-213 (Clinical Unit), T.T.C. Industrial Area, Mahape M.I.D.C., Navi Mumbai.
Thane
MAHARASHTRA
400710
India |
| Phone |
02227781889 |
| Fax |
02227781884 |
| Email |
yashvant.khaire@raptimresearch.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Yashvant Khaire |
| Designation |
Clinical Investigator |
| Affiliation |
Raptim Research Pvt. Ltd. |
| Address |
Raptim Research Private Limited
A-226, PAP-213 (Clinical Unit), T.T.C. Industrial Area, Mahape M.I.D.C., Navi Mumbai.
MAHARASHTRA
400710
India |
| Phone |
02227781889 |
| Fax |
02227781884 |
| Email |
yashvant.khaire@raptimresearch.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Yashvant Khaire |
| Designation |
Clinical Investigator |
| Affiliation |
Raptim Research Pvt. Ltd. |
| Address |
Raptim Research Private Limited
A-226, PAP-213 (Clinical Unit), T.T.C. Industrial Area, Mahape M.I.D.C., Navi Mumbai.
MAHARASHTRA
400710
India |
| Phone |
02227781889 |
| Fax |
02227781884 |
| Email |
yashvant.khaire@raptimresearch.com |
|
|
Source of Monetary or Material Support
|
| Lupin Research Inc. 111 S Calvert St Ste 2100 Baltimore, MD 21202 |
|
|
Primary Sponsor
|
| Name |
Lupin Research Inc |
| Address |
111 S Calvert St Ste 2100 Baltimore, MD 21202 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
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 Yashvant Khaire |
Raptim Research Pvt. Ltd. |
A-226, PAP-213 (Clinical Unit) T.T.C., Industrial Area, Mahape M.I.D.C.,
Thane
MAHARASHTRA |
02227781889
02227781884
yashvant.khaire@raptimresearch.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Sai 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 |
Healthy |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
LSP-5415 |
LSP-5415 (etonogestrel/ethinyl estradiol vaginal ring) delivers 0.12 mg/0.010 mg per day.
|
| Comparator Agent |
NuvaRing® |
NuvaRing® (etonogestrel/ethinyl estradiol vaginal ring) delivers 0.12 mg/ 0.015 mg/day
|
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
40.00 Year(s) |
| Gender |
Female |
| Details |
1. Must be able, and willing, to sign Informed Consent Form prior to
study participation in accordance with legal requirements.
2. Females (18 to 40 years of age, inclusive) without uncontrolled
concomitant disease at Baseline Visit.
3. Have a regular menstrual cycle that is 24-32 days in duration.
4. Body Mass Index (BMI) of 18 kg/m2 to 30 kg/m2.
5. Will not be at risk for pregnancy, subjects must agree to consistently use reliable non-hormonal contraceptive methods (spermicide-coated condoms, male partner’s sterilization via vasectomy, or sexual abstinence), or be in a same-sex relationship from screening through study completion, or be surgically sterilized by bilateral tubal ligation.
6. Subjects must be in good physical and mental health as determined by vital signs, medical history.
7. Subjects must have a Blood Pressure reading in a sitting position,
between 90-140 mmHg (systolic) and 50-90 mmHg (diastolic) and
pulse rate between 50 and 100 bpm.
8. Be at least 3 months after a delivery or abortion.
9. Willing to abstain from vaginal products e.g., tampons, intravaginal medications etc. during the ring wear period for the study duration except water based vaginal lubricants/spermicides. |
|
| ExclusionCriteria |
| Details |
1. Pregnancy, a positive serum ß-hCG pregnancy test at screening or
lactation.
2. Use of tobacco- or nicotine-containing products within 6 months prior to check-in on Day 1.
3. history of cervical carcinoma or other carcinomas of the vagina or vulva.
4. history of breast cancer or any hormonally sensitive cancer.
5. Subjects with abnormal pap smears that require colposcopic
evaluations as defined by the fourth American Society of Colposcopy and Cervical Pathology sponsored guidelines for management of cervical cancer abnormalities during the next 6
months are excluded until they have undergone colposcopic
evaluation which has determined that a cervical procedure is not
necessary during the 6 months following the colposcopy.
6. History of thrombophlebitis, venous or arterial thromboembolic
diseases.
7. Any known severe neurological, gastrointestinal, hepatic or other
disease that might interfere with the intake of an investigational drug
or any study condition.
8. Clinically relevant findings from serum biochemistry and hematology and HBsAg and C Virus/HIV serology.
9. Clinically relevant/significant ECG findings.
10. Additional contraindications related to the use of ethinyl estradiol (EE), or hormonal contraceptives including women with a high risk of arterial or venous thrombotic diseases. Have cerebrovascular disease, coronary artery disease, thrombogenic valvular or thrombogenic rhythm diseases of
the heart, inherited or acquired hypercoagulopathies, uncontrolled hypertension, diabetes mellitus with vascular disease, headaches with focal neurological symptoms or migraine headaches with aura 11. History of migraine with focal neurological symptoms.
12. Known hereditary or acquired predisposition for venous and or
arterial thromboembolism.
13. Less than 2 weeks remobilization after major surgery or prolonged immobilization
14. Alcohol, drug, or medicine abuse, or suspicion thereof.
15. Known allergy to any ingredient of the investigational drug.
16. Use of long acting injectable or implant hormonal therapy. A
washout period of 10 months and two regular cycles is required for
long-acting injectable contraceptive therapy or implant hormonal
therapy prior to the start of screening.
17. Use of hormonal or non hormonal IUDs within 30 days prior to the start of screening.
18. Participation in another clinical trial at same time or within the
preceding three months
19. Not fulfilling study specific requirements at screening.
20. Subjects desire to become pregnant during the Study.
21. Undiagnosed vaginal discharge/bleeding, vaginal lesions/
abnormalities or undiagnosed abnormal uterine bleeding. Subjects
suspected of having a vaginal infection may be enrolled after treatment and subsequent negative test results; partner treatment is also recommended.
22. Regular intake or use of the following medication:
a. any drugs that might interfere with the investigational drug.
b. any hormonal preparation 30 days prior to the start of screening.
c. any drugs known to induce liver enzymes.
e. any broad-spectrum antibiotics.
f. use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
Area under the plasma concentration-time curve from time zero to 28 days post dose (AUC0-28d) for ENG.
From time zero to the last measurable concentration (AUC0-last) for ENG
From time zero to infinity (AUC0-inf) for ENG maximum observed plasma concentration (Cmax) for ENG |
0, 1, 2, 4, 8, 12 hrs on Day 1, 2 (24 hrs), 3 (48 hrs), 5 (96 hrs), 7 (144 hrs), 9 (192 hrs), 12 (264 hrs), 14 (312 hrs), 18 (408 hrs), 21 (480 hrs), 24 (552 hrs), 26 (600 hrs), 28 (648 hrs), 29 (672 hrs, immediately before ring removal), Day 29 (1, 2, 4, 8, 12 hrs postremoval), Day 30 (24 hours post-removal), Day 31 (48 hrs post-removal) Day 32 (72 hrs post-removal), Day 33 (96 hours post-removal), Day 34 (120 post-removal hours), Day 35 (144 hrs post-removal), Day 36 (168 hrs post-removal) |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
time to maximum observed plasma concentration (tmax) for ENG
Area under the plasma concentration-time curve from time zero to 21 days (AUC0-21d)
Area under the plasma concentration-time curve from time zero to 26 days (AUC0-26d)
Kel, terminal elimination rate constant
Half-life, T1/2 |
0, 1, 2, 4, 8, 12 hrs on Day 1, 2 (24 hrs), 3 (48 hrs), 5 (96 hrs), 7 (144 hrs), 9 (192 hrs), 12 (264 hrs), 14 (312 hrs), 18 (408 hrs), 21 (480 hrs), 24 (552 hrs), 26 (600 hrs), 28 (648 hrs), 29 (672 hrs, immediately before ring removal), Day 29 (1, 2, 4, 8, 12 hrs postremoval), Day 30 (24 hours post-removal), Day 31 (48 hrs post-removal) Day 32 (72 hrs post-removal), Day 33 (96 hours post-removal), Day 34 (120 post-removal hours), Day 35 (144 hrs post-removal), Day 36 (168 hrs post-removal) |
|
|
Target Sample Size
|
Total Sample Size="40"
Sample Size from India="40"
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
|
Phase 2 |
|
Date of First Enrollment (India)
|
24/03/2022 |
| 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="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
Not Applicable |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Lupin is developing LSP-5415, a contraceptive vaginal ring (CVR) containing 9 mg etonogestrel (ENG) and 1 mg ethinyl estradiol (EE), which releases an average of 0.12 mg/day of ENG and 0.010 mg/day of EE, intended for continual contraceptive delivery over 26 days followed by a 2-day, ring-free interval within a 28-day menstrual cycle. LSP-5415 is intended to be similar to NuvaRing (a polymeric vaginal ring containing 11.7 mg ENG and 2.7 mg EE, which releases an average of 0.12 mg/day of ENG and 0.015 mg/day of EE for 21-day duration of activity and 7 day ring free interval) based on dosage form and ENG dose. LSP-5415 is a vaginal ring with a lower dose of EE and a longer treatment duration (26 days and a 2 day ring free interval) than available in currently approved vaginal rings. |