Official Title: “A Study of Continuous Oral Contraceptives and Doxycycline”

The purpose of this study is to learn if the study drug, doxycycline, can decrease the amount of unplanned vaginal bleeding that women commonly experience when taking combined oral contraception (pills with estrogen and progestin) in a continuous fashion (no hormone-free week). The study drug, doxycycline, is an antibiotic used commonly for many conditions (i.e.

acne, Chlamydia infections, pneumonia) and can be safely used on a daily basis. Doxycycline has been shown to decrease unplanned vaginal bleeding in progestin-only contraception but has not been studied in combined hormonal contraception.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Factorial Assignment, Efficacy Study

Study Primary Completion Date: May 2009

We intend to conduct a prospective, randomized, placebo controlled, double blind study at Oregon Health and Science University. This study will be conducted over four 28-day cycles (112 days of active COC hormone). All women enrolled in the study will take the same daily low dose COC. This protocol will be divided into two studies, a bleeding study and an endometrial biopsy study, each with two treatment arms; typical dose doxycycline (Arm 1), and CRSD (Arm 2).

The first arm (Arm 1) of this study will constitute the typical dose doxycycline arm. In this arm, there will be two study groups. Group 1, the treatment group, will take doxycycline 100 mg orally twice a day for five days starting on the first day of bleeding if breakthrough bleeding occurs. The control group will take a placebo orally twice a day for five days starting on the first day of bleeding if breakthrough bleeding occurs. After three months, both groups will stop doxycycline (or placebo) and will continue on a COC alone for the remaining 28 days of the study.

The second arm (Arm 2) of the study will constitute the CRSD doxycycline arm. Subjects in this arm of the study will be divided into Group 3 and Group 4. Group 3 will take CRSD doxycycline (40mg) daily for three months. Group 4 will take a daily placebo. Similarly to the first arm of the trial, after three months, both groups will stop doxycycline (or placebo) and will continue in a COC alone for the remaining 28 days of the study.

This study also includes a endometrial biopsy sub-study: At the time of recruitment we will identify participants who are willing to undergo endometrial biopsy during the study period.

These subjects will constitute a separate cohort who will enroll in the prospective, randomized, double blind, placebo controlled endometrial biopsy study.

Intervention(s) in this Clinical Trial

• Drug: Lybrel
  • All women enrolled in the study will take the same daily low dose oral contraceptive (20-mcg EE/90 mcg LNG) dosed in a continuous fashion.
• Drug: Doxycycline
  • 100 mg orally twice a day for five days starting on the first day of breakthrough bleeding. This regimen will be repeated if bleeding persists or recurs seven days after completing five-day course of doxycycline.
• Drug: Oracea
  • 40-mg tablet daily for 84 days
• Drug: Placebo
  • Placebo pill orally twice a day for five days starting on the first day of breakthrough bleeding. This regimen will be repeated if bleeding persists or recurs seven days after completing five-day course of placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Placebo Comparator: 2
• Experimental: 3
• Placebo Comparator: 4

Primary Measures

• Differences in bleeding patterns between study groups.
  • Time Frame: After enrollment is complete
    Safety Issue?: No

Secondary Measures

• Subject satisfaction.
  • Time Frame: After enrollment is complete
    Safety Issue?: No
• Subject compliance
  • Time Frame: After subject particpation is complete
    Safety Issue?: No

Inclusion Criteria:

• General good health
• Willing and able to agree to randomization and sign informed consent
• Currently having regular menstrual cycles (24-36 days), with combined cyclic hormonal method (COCs, Nuva Ring, Ortho Evra), without intermenstrual bleeding in last 2 years.

Exclusion Criteria:

• IUD in place
• Abnormal pap smear that has not been treated or followed up
• Those with hypersensitivity reactions to doxycycline or any of the tetracyclines
• Use of depomedroxyprogesterone acetate within 9 months of the start of the study.
• Use of hormonal medications (excluding cyclic contraceptives and plan B) within 2 months of the start of the study.
• Any one unwilling to keep a daily menstrual diary or otherwise unwilling to follow the study criteria
• Currently taking medications that interfere with COCs (rifampin, carbemazepine, St.
• Johns wort)
• Currently has a progestin implant
• Positive Gonorrhea or Chlamydia cultures at enrollment examination
• Smoking more than 5 cigarettes per month
• Any medical condition that is a contraindication to the use of COCs in accordance with product labeling including:
• History of thrombophlebitis, deep venous thrombosis, thrombogenic vasculopathies, thrombogenic rhythm disorders or thromboembolic disorders
• Current or past history of cerebrovascular or coronary artery disease
• Scheduled major surgery in the next six months with prolonged immobilization
• Diabetes with vascular involvement
• Headache with focal neurologic symptoms
• Uncontrolled hypertension
• Suspected or known carcinoma of the breast or personal history of breast cancer
• Carcinoma of the endometrium or other known or suspected estrogen dependent neoplasms
• Undiagnosed genital bleeding
• History of cholestatic jaundice of pregnancy or cholestatic jaundice with prior oral contraceptive use
• Hepatic adenoma or carcinoma or active liver disease if liver function has not returned to normal
• Known or suspected pregnancy
• Hypersensitivity to estrogen or progesterone containing products

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Oregon Health and Science University

Overall Clinical Trial Officials and Contacts

Jeffrey T Jensen, M.D, MPH Principal Investigator Oregon Health and Science University  

Overall Contact: Women's Health Research Unit Confidential Recruitment Line 503 494-3666 whru@ohsu.edu

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00480532

Study ID Number: OHSU FAMPLAN 2907

ClinicalTrials.gov Identifier: NCT00480532

Health Authority: United States: Food and Drug Administration

Women's Health Research Unit website