CTRI/2022/06/043170 [Registered on: 10/06/2022] Trial Registered Prospectively
Last Modified On:
15/07/2022
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
NA
Study Design
Other
Public Title of Study
Pharmacokinetic and Pharmacodynamic study
Scientific Title of Study
A Study to Evaluate the Effect of a Contraceptive Vaginal Ring LSP-5415 Releasing Ethinyl Estradiol plus Etonogestrel on Ovarian Function in Healthy Adult Females
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CVR-WH-202 Version No. 2.0, Date 04-APR-2022
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 Pvt. Ltd.,
PAP-213, PAP-A-218 and PAP-A-219 (Screening Facility),
A-226 (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 Pvt. Ltd.,
PAP-213, PAP-A-218 and PAP-A-219 (Screening Facility),
A-226 (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 Pvt. Ltd.,
PAP-213, PAP-A-218 and PAP-A-219 (Screening Facility),
A-226 (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
Name
Address
Nil
NA
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.
PAP-213, PAP-A-218 and PAP-A-219 (Screening Facility),
A-226, (Clinical Unit )T.T.C. Industrial Area, Mahape M.I.D.C.,
Navi Mumbai Thane MAHARASHTRA
LSP-5415 (etonogestrel/ethinyl estradiol vaginal ring) is a contraceptive vaginal ring, intended for continual contraceptive delivery over 26 days followed by a 2-day, ring-free interval within a 28-day menstrual cycle.
Comparator Agent
No Comparator Agent for this study.
NIL, No Comparator Agent for this study.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
35.00 Year(s)
Gender
Female
Details
Must be able to read and write and willing to sign Informed Consent Form prior to study participation in accordance with legal requirements.
2. Females (18 to 35 years of age, inclusive) without uncontrolled concomitant disease at the Baseline Visit.
3. Have a regular menstrual cycle that is 24-32 days in duration.
4. Cohort #1 - BMI of 18 kg/m2 to 30 kg/m2, inclusive. Cohort #2 - BMI > 30 kg/m2 to ≤ 35 kg/m2.
5. Will not be at risk for pregnancy; subjects must agree to consistently use reliable non-hormonal contraceptive methods (spermicide-coated condoms, sterilization, 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. Both ovaries and uterus must be intact, and visible on transvaginal ultrasound (TVUS) examination during screening.
7. Subjects must be in good physical and mental health as determined by vital signs, medical history and clinical examination.
8. 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.
9. Be at least 3 months after a delivery or abortion.
10. Be at least six months since last progestin injection with one or more spontaneous menses.
11. 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 β-hCG pregnancy test at screening or lactation.
2.Use of tobacco- or nicotine-containing products within 6 months prior to study drug administration on Day 1 of treatment cycle 1.
3. Have a history of cervical carcinoma or other carcinomas of the vagina or vulva.
4. Subjects with abnormal pap smears that require colposcopic evaluations as defined by the fourth American Society of Colposcopy and Cervical Pathology (ASCCP) sponsored guidelines for management of cervical cancer abnormalities during the next 6 months are excluded. Subjects with abnormal pap smear and who have undergone colposcopic evaluation which has determined that a cervical procedure is not necessary during the 6 months following the colposcopy are allowed.
5. Breast cancer or other estrogen- or progestin-sensitive cancer, now or in the past.
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. Planned surgical procedures during the study period.
9. Clinically relevant/significant findings from serum biochemistry and hematology and HBsAg and C Virus/HlV serology as evaluated by the investigator.
10. Clinically relevant electrocardiogram findings.
11. An ovulatory pre-treatment cycle, or no ovulation by Day 27 of the pre-treatment cycle, or sonographical peculiarities concerning the ovarian status, that have not disappeared during the pre-treatment cycle.
12. Ovarian cyst larger than 3 cm in largest dimension on TVUS that persists during the pre-treatment ovulatory cycle.
13. Additional contraindications related to the use of ethinyl estradiol, or hormonal contraceptives including women with a high risk of arterial or venous thrombotic diseases. Examples include women who are known to: Have cerebrovascular, coronary artery, thrombogenic valvular or thrombogenic rhythm, inherited or acquired hypercoagulopathies, Have uncontrolled hypertension, diabetes mellitus, headaches with focal neurological symptoms or migraine headaches with aura
14. History of migraine with focal neurological symptoms.
15. Known hereditary or acquired predisposition for venous and/or arterial thromboembolism.
16. Less than 2 weeks remobilization after major surgery or prolonged immobilization.
17. Alcohol, drug, or medicine abuse, or suspicion thereof.
18. Known allergy to any ingredient of the investigational drug.
19. Use of long-acting injectable or implant hormonal therapy. A washout period of 10 months and two regular cycles is required after use of long-acting injectable contraceptive therapy or implant hormonal therapy prior to the pre-treatment cycle.
20. Use of hormonal or non-hormonal Intrauterine devices within 30 days prior to the start of the pre-treatment cycle.
21. Participation in another clinical trial at same time or within the preceding three months.
22. Subjects with a desire to become pregnant during the study.
23. Undiagnosed vaginal discharge, 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.
24.Regular intake or use of the following medication:
Any drugs that might interfere with the investigational drug, any hormonal preparation, any drugs known to induce liver enzymes, any drugs known to inhibit CYP 3A4, any broad-spectrum antibiotics, any Hepatitis C drug.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
The proportion of subjects in Cohort 1 with complete ovarian inhibition over the entire treatment period (3 treatment cycles). Ovarian inhibition will be assessed by rating the suppression of ovaries using the Hoogland score (Hoogland HJ, Skouby SO, 1993). This score is based on The follicular size assessed by transvaginal ultrasound (TVUS).
Endogenous hormone levels: serum Estradiol (E2), and serum Progesterone (P).
A Hoogland and Skouby grade 3 and below represents ovulation inhibition.
Cycle1 Predose,1,2,6,8hrs on Day1,4,6,8,12,14,18,22,26,27, 6hrs post-removal and Day28. Cycle2 Predose, 4 hrs on Day1,4,8,14,22,26,27, 6 hrs post-removal and Day28 (24hrs postremoval). Cycle3 Predose,1,2,6,8hrs on Day1, 4, 6, 8, 12, 14, 18, 22, 26, 27, 6hrs postremoval,Day28(24hrs postremoval) and 29 (48hrs postremoval). For SHBG will be collected pre-insertion on Cycle1, Day1 and pre-removal on Cycle3, Day27.
Secondary Outcome
Outcome
TimePoints
Serum level of Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), E2, P. -Plasma levels of EE, ENG: blood samples will be taken at regular time points during Cycle 1, 2 and 3 (26-day wear period).-Samples for sex hormone-binding globulin (SHBG) will be collected pre-insertion on Cycle 1, Day 1 and pre-removal on Cycle 3, Day 27.-Safety parameters including adverse events, clinical laboratory parameters, and vital sign measurements.
Cycle1:Predose,1,2,6,8hrs onDay1,4,6,8,12,14,18,22,26,27, 6hrs post-removal and 28. -Cycle2 Predose, 4 hrs on Day1,4,8,14,22,26,27,6 hrs post-removal and Day28 (24hrs postremoval). -Cycle3 Predose,1,2,6,8hrs on Day1,4,6,8,12,14,18,22,26,27,6hrs postremoval,Day28 (24hrs postremoval) and29 (48hrs postremoval). -For SHBG will be collected pre-insertion on Cycle1, Day1 and pre-removal on Cycle3, Day27.
Target Sample Size
Total Sample Size="26" Sample Size from India="26" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
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) containingetonogestrel(ENG)andethinylestradiol(EE), intended for continual contraceptive delivery over a 28-day menstrual cycle.