A Pivotal, Multicenter, Non-Comparative Trial on the Contraceptive Efficacy, Safety, Tolerability of LPRI-424, 13 Cycles

Sponsor

Insud Pharma (Industry)

Overall Status

Unknown status

CT.gov ID

NCT03945513

Collaborator

Chemo Research (Industry)

995

Enrollment

Location

Arm

21.9

Anticipated Duration (Months)

45.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main objective of this trial is to demonstrate the contraceptive efficacy of LPRI424, Additional goals of the trial are to demonstrate the safety and tolerability of LPRI424.

Condition or Disease	Intervention/Treatment	Phase
Contraception	Drug: LPRI424 (dienogest/ethinylestradiol)	Phase 3

Detailed Description

This trial is a prospective, multicenter, open-label, non-controlled trial in postmenarcheal and premenopausal female subjects, including adolescents, between the ages of 15 and 45 who present to the clinic seeking contraception.

At screening, informed consent will be obtained and the screening procedures will be performed. After confirmation of the subject's eligibility, the subject will be provided with the investigational product and trained in the use of an electronic diary. Afterwards, the subjects will attend visit the clinical site on Day 20±2 of the 1st, 3rd, 6th and 9th cycles and on Day 29+2 of the 13th cycle. The last clinical site visit will occur 10-14 days after the 13th cycle visit.

The trial will include women who have never used hormonal contraceptives before consent (naïve users), women who have used hormonal contraceptives in the past but have had a contraceptive-free period before consent and a full menstrual cycle during the drug-free period (previous users) as well as women directly switching from another hormonal method (switchers).

Adverse events and safety information will be collected throughout the study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

995 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pivotal, Multicenter, Non-Comparative Trial on the Contraceptive Efficacy, Safety, Tolerability of LPRI-424( Dienogest 2.00 mg / Ethinyl Estradiol 0.02 mg) During 13 Cycles

Actual Study Start Date :

Dec 3, 2019

Anticipated Primary Completion Date :

Oct 1, 2021

Anticipated Study Completion Date :

Oct 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LPRI424	Drug: LPRI424 (dienogest/ethinylestradiol) One LPRI424 tablet once per day for 24 days followed by 4 placebo tablets for 4 days equals one cycle.

Arm

Intervention/Treatment

Experimental: LPRI424

Drug: LPRI424 (dienogest/ethinylestradiol)

One LPRI424 tablet once per day for 24 days followed by 4 placebo tablets for 4 days equals one cycle.

Outcome Measures

Primary Outcome Measures

Number of pregnancies (evaluable cycles) [up to 13 months]
Pearl index (PI) from evaluable cycles in non-breastfeeding women aged ≤ 35 years (at the time of trial enrollment)

Secondary Outcome Measures

Number of pregnancies (all) [up to 13 months]
Pearl Index based on overall cycles (overall PI) in women aged ≤ 35 years (at the time of trial enrollment)
Number of pregnancies (method failures) [up to 13 months]
PI for method failures in women aged ≤ 35 years (at the time of trial enrollment)
Pregnancy ratio [up to 13 months]
Pregnancy ratio in women aged ≤ 35 years (at the time of trial enrollment)
Overall PI, PI for method failures [Up to 13 months]
Overall PI, PI for method failures, PI (using evaluable cycles) and pregnancy ratio (life table analysis) in all women
Overall PI, PI for method failures [Up to 13 months]
5. Overall PI, PI for method failures, PI (using evaluable cycles) and pregnancy ratio (life table analysis) in women aged > 35 years
Number of participants with adverse events as a measure of safety [Up to 13 months]
Adverse events and changes in vital signs, clinical laboratory parameters
Tolerability; Vaginal bleeding pattern [Up to 13 months]
Vaginal bleeding pattern

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Sexually active, postmenarcheal and premenopausal female subjects at risk of pregnancy aged between 15-45 years (inclusive).

Female subjects at risk of pregnancy aged between 15 and 17 years (inclusive) provided that:

Applicable national, state and local laws allow subjects in this age group to consent/assent to receive contraceptive services,
All applicable laws and regulations regarding the informed consent/assent of the subjects to participate in clinical trials are observed.
Women who:
have never used hormonal contraceptives before consent/assent (naïve users),
have used hormonal contraceptives in the past, but have had a hormonal contraceptive-free period before consent/assent and a full menstrual cycle during the drug-free period (previous users)
directly switch from another hormonal contraceptive (switchers).
Only for subjects who did not use hormonal contraception during the last six months before consent/assent: Regular cycles (i.e. cycle length between 24 and 35 days) during the last six months.
At least three complete menstrual cycles after delivery pregnancy (only applicable for women who were pregnant within the last six months).
At screening, maximum systolic blood pressure ≤ 140 mm Hg and diastolic blood pressure ≤ 90 mm Hg.
Be able and willing to provide written informed consent or assent if the subject is adolescent, prior to undergoing any trial-related procedure.
Willing to use trial contraception for thirteen 28-day cycles.
Be willing to have intercourse in each cycle of the trial without the need to use back-up contraceptive.
Be willing to state that, to her best knowledge, her male sexual partner(s):
Has not had a vasectomy or been previously diagnosed as infertile.
Has not been previously diagnosed or suspected of human immunodeficiency virus (HIV) unless he has subsequently had a negative HIV test.
Has not been known to have engaged in homosexual intercourse in the past five years unless he has had negative HIV test results since then.
Has not shared injection drug needles in the past unless he has had a negative HIV test at least six weeks since last use.
Agree not to participate in any other clinical trials during the course of this trial (participation in a non-interventional study is allowed).

Exclusion Criteria:

Pregnancy, wish for pregnancyt or breastfeeding subjects.
Subject is known to or suspected of not being able to comply with the trial protocol, the use of the trial medication or the use of the trial diary.
History of infertility.
Abnormal finding on pelvic, breast or ultrasound examination that in the investigator's opinion contraindicates participation in the trial.
Unexplained amenorrhea.
Known polycystic ovary syndrome (PCOS).
Women ≥21 years of age with a Papanicolaou (pap) smear reading LGSIL or higher at screening (or six months prior to screening date). Subjects with atypical squamous cells of undetermined significance (ASC-US) can be included if they are negative for high-risk Human human papilloma virus (HPV) strains. Subjects <21 years of age do not require a pap smear.
Known contraindication or hypersensitivity to ingredients or excipients of the IMP, including:
Presence or risk of a venous thromboembolism (VTE)
Venous thromboembolism - existing VTE (even under treatment with anticoagulants) or history of VTE* (e.g., deep venous thrombosis [DVT] or pulmonary embolism [PE])

*including a positive family history (VTE ever in a sibling or parent in particular at an age before 50 years)

Known hereditary or acquired predisposition for VTE, e.g., activated protein C (APC) resistance (including Factor V Leiden), antithrombin III deficiency, protein C deficiency or protein S deficiency
Major surgery with prolonged periods of immobilization
High risk of venous thromboembolism due to the presence of multiple risk factors
Presence or risk of an arterial thromboembolism (ATE)
Arterial thromboembolism - existing ATE, history of ATE (e.g., myocardial infarction) or prodromal condition (e.g., angina pectoris)
Cerebrovascular disease - existing stroke, stroke or prodromal disorder (e.g., history of transient ischemic attack [TIA])
Known hereditary or acquired predisposition for ATE, e.g., hyperhomocysteinemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulants)
History of migraine with focal neurological symptoms
High risk of arterial thromboembolism due to multiple risk factors or to the presence of one serious risk factor such as diabetes mellitus with vascular damage, severe hypertension, severe dyslipoproteinemia, smokers or existing or previous pancreatitis, if it is associated with severe hypertriglyceridemia
Existing or previous liver diseases in which liver function has not returned to normal (also Dubin-Johnson and Rotor syndrome)
Existing or previous liver tumors
Known or suspected sex hormone-dependent malignant tumors (e.g., breast or endometrium)
Unexplained vaginal bleeding
Hypersensitivity to the active ingredients or any of the excipients
Concomitant use with the medicinal products containing ombitasvir/paritaprevir/ ritonavir and dasabuvir.
Uncontrolled thyroid disorder (i.e., on stable dose of thyroid replacement for less than two months at the time of assent/consent).
Uncontrolled concomitant diseases (i.e., not on a stable treatment dose for at least two months at the time of assent/consent).
Evidence or history of alcohol, medication or drug abuse (within the last 12 months prior to consent/assent) or medication abuse (within the last three months prior to consent/assent).
Predisposition bruising within the last 12 months prior to consent/assent.
Known or suspected HIV, hepatitis and/or HPV infection (if the infection is due to aggressive strains) at screening.
Received a dose of depot medroxyprogesterone acetate (DMPA or Depo-Provera®) during the 10 months prior to consent/assent, or received any combined injectable contraceptive (e.g., Cyclofem®) during the six months prior to consent/assent, or no spontaneous menses since last injection.
Long-term treatment (longer than seven consecutive days within a month prior to V1b) of any medication that might interfere with the efficacy of hormonal contraceptives, e.g.:
Anticonvulsants (e.g. phenytoin, carbamazepine, oxcarbazepine, topiramate, felbamate)
Barbiturates (e.g. primidone)
Some antibiotics (such as rifampicin)
HIV medication (such as ritonavir, neviparine and efavirenz)
Bosentan
Griseofulvin
St. John's wort (hypericum perforatum)
Metoclopramide
Prohibited medication including the regular intake or use of estrogens, progestogens, activated charcoal, microsomal enzyme-inducing drugs
Administration of human chorionic gonadotropin (hCG) or intake of co-medication containing hCG within a month prior to V1b).
Progestin-releasing intra-uterine device (IUD) or contraceptive implant received or in place within the last two months prior to consent/assent.
Planned regular concomitant use of barrier contraceptive methods, spermicides, IUDs or other contraceptive measures (except occasional use for safety reasons, e.g., to reduce risk of infection).
Evidence or history of clinically significant psychiatric illness, such as major depression or schizophrenia, that in the investigator's opinion contraindicates participation in the trialor suicide risk.
Planned surgery during the anticipated time of participation in this trial requiring withdrawal of an oral contraceptive.
Participation in another trial of an investigational drug or device parallel to the current trial or less than 90 days before consent/assent, or previous participation in the current trial and dispensed trial medication.
Subject is a member of the investigator's or sponsor's staff or a relative or family member thereof.
Any condition that, in the opinion of the investigator, may jeopardize protocol compliance or the scientific integrity of the trial.