A Phase I Study in Young Healthy Women to Investigate the Effects of Laquinimod on Standard Oral Contraceptive When Both Treatments Are Given Together

NCT02085863 | Completed Phase 1 DMC

• 2 other identifiers: TV5600-PK-100172013-005356-14
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, randomized, double blind, placebo controlled, 2-way crossover drug-drug interaction (DDI) study to assess the effect of laquinimod on the PK and PD of ethinylestradiol (EE) and levonorgestrel (LNG) a commonly used oral contraceptive combination.

Conditions

Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (2)

• AUC0-24 of EE and LNG plasma concentrations.

  to assess the effect of once daily oral doses of laquinimod on the pharmacokinetics (PK) of ethinylestradiol (EE) and levonorgestrel (LNG)

  10 min prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours postdose

• Cmax of EE and LNG plasma concentrations.

  to assess the effect of once daily oral doses of laquinimod on the pharmacokinetics (PK) of ethinylestradiol (EE) and levonorgestrel (LNG

  10 min prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours postdose

Secondary Outcomes (11)

• Tmax of EE and LNG plasma concentrations

  10 min prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours postdose

• Cmax of laquinimod plasma concentrations

  10 min prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours postdose

• AUC0-24 of progesterone

  10 min prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours postdose

• Ctrough of luteinizing hormone [LH], and follicle-stimulating hormone [FSH]

  10 min prior to dosing

• Summary of Participants with Adverse Events

  25 Weeks

Study Arms (2)

Laquinimod

EXPERIMENTAL

once daily oral doses of laquinimod (with combination oral contraceptives)

Drug: laquinimod; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Matching placebo (with combination oral contraceptives)

Drug: laquinimod; Drug: Placebo

Interventions

laquinimod DRUG

Oral laquinimod 0.6 mg capsules (with oral contraceptives tablets containing 30 μg ethinylestradiol and 150 μg levonorgestrel (Microgynon®)

Also known as: TV5600

Laquinimod; Placebo

Placebo DRUG

Placebo (with oral contraceptives tablets containing 30 μg ethinylestradiol and 150 μg levonorgestrel (Microgynon®)

Laquinimod; Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Pre-menopausal women of age 18 to 40 years, who are healthy, non-pregnant and not planning pregnancy within the study period.
• Women of childbearing potential who are willing to continuously use the oral contraceptive (OC) product containing EE 30 μg and LNG 150 μg from at least the commencement of their last normal period prior to the first dose of study medication and for a total of 4 consecutive cycles.
• Willing to use a double barrier method of contraception (condom or diaphragm with spermicide) from screening until 30 days after the last laquinimod/placebo treatment. During administration of OC, the double barrier method should also be used.
• Body Mass Index ranging from 18-30 kg/m2, inclusive.
• Must be in a good health as determined by medical history, electrocardiogram (ECG), vital signs, physical and gynecological examination, and clinical laboratory tests.
• Must have a regular menstrual cycle of 25 to 35 days (28-3/+7days) in the preceding 3 months prior to screening.
• Subjects must be able to understand the requirements of the study and be willing to comply with the requirements of the study (eg, all dietary, exercise, tobacco and alcohol restrictions) and provide their written informed consent to participate in the study.

You may not qualify if:

• Subjects who smoke at any frequency, have smoked in the last 6 months, or are planning to start smoking during the study, tobacco users, subjects currently using nicotine products (patches, gums, etc.) or subjects with a positive urine cotinine test at screening and/or at day -7.
• Subjects with a known drug hypersensitivity to laquinimod, or one of its excipients (ie, mannitol, meglumine, or sodium stearyl fumarate).
• Subjects with any significant food/drug allergies at the discretion of the investigator.
• Subjects who are pregnant or lactating.
• Subjects who had one of the following conditions in the noted amount of time prior to screening or at any time between screening and day -7: o Major trauma or surgery in the past 2 months.
• Acute infection within 2 weeks (14 days).
• Any malignancies, excluding basal cell carcinoma, prior to randomization.
• Subjects who have any condition that possibly interferes with drug absorption, distribution, metabolism, or excretion.
• Subjects suffering from, or with history of, one of the following: cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s), or a history of any illness that, in the opinion of the Investigator, might pose additional risk to the subject by participation in the study or confound the results of the study.
• Subjects suffering from any condition in which the OC is contra indicated or not recommended.
• Subjects who have used patches/intrauterine device/injectable hormonal contraception within 6 month prior to screening.
• History of irregular menstruation.
• Subjects with clinically relevant abnormality (judged by the investigator) of serum electrolytes or complete blood count.
• Serum levels of ≥2× upper limit of normal alanine aminotransferase or aspartate aminotransferase or gamma-glutamyltransferase or alkaline phosphatase or direct bilirubin.
• Subjects who have used one of the forbidden drugs or foods as following: o Excessive amounts (defined as daily intake of alcohol \>40 g) of alcoholic beverages (eg, beer, wine, distilled spirits), or have a history of alcohol abuse, or are unwilling to comply with the restricted use of alcoholic beverages during the study.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (1)

Teva Investigational Site 32415

Mönchengladbach, Germany

Location

MeSH Terms

Interventions

laquinimod

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2014
• First Posted: March 13, 2014
• Study Start: February 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: November 1, 2014
• Last Updated: November 9, 2021

Record last verified: 2021-11

Locations

DE (1)