Treatment of Endometriosis With Norethindrone Acetate ( NA) VS. Gonadotropin- Releasing Hormone (GnRH) Agonist (Lupron Depot 11.25 mg)

Original Study ID : 1RO1HD43281

NCT ID : NCT00458458

Brief Title : Treatment of Endometriosis With Norethindrone Acetate ( NA) VS. Gonadotropin- Releasing Hormone (GnRH) Agonist (Lupron Depot 11.25 mg)

Official Title : Treatment of Endometriosis With Norethindrone Acetate ( NA) VS. Gonadotropin- Releasing Hormone (GnRH) Agonist (Lupron Depot 11.25 mg)

Brief Summary : (A) Major 1) to compare the effectiveness of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3) in relieving symptoms of endometriosis, 2) to compare bone density in the two treated groups in order to demonstrate that NA does not affect bone density; (B) Minor: 1) To compare the lipid profiles of patients in the two groups to confirm the hypothesis that the effects of NA and GnRH agonists on lipid profiles are similar, 2) To determine whether quality of life, assessed by questionnaire, is better in patients assigned to NA than in patients assigned to GnRH, 3) To determine whether NA has fewer adverse effects than GnRH agonist.

Source : Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Detailed Description :
Objectives: (A) Major 1) to compare the effectiveness of norethindrone acetate (NA) with GnRH
agonist (Lupron-Depot-3) in relieving symptoms of endometriosis, 2) to compare bone density
in the two treated groups in order to demonstrate that NA does not affect bone density; (B)
Minor: 1) To compare the lipid profiles of patients in the two groups to confirm the
hypothesis that the effects of NA and GnRH agonists on lipid profiles are similar, 2) To
determine whether quality of life, assessed by questionnaire, is better in patients assigned
to NA than in patients assigned to GnRH, 3) To determine whether NA has fewer adverse effects
than GnRH agonist.

After signing an IRB approved consent from 112 women with symptomatic endometriosis,
diagnosed surgically, will be treated with NA or Lupron-Depot-3 for 24 weeks. After 24 weeks
both groups will be treated only with NA until 52 weeks. After that, both groups will be
followed for an additional 52 weeks to assess any return of clinical symptoms and to
determine whether laboratory tests of drug related changes return to pretreatment levels.

Treatment regimens are as follows: For the first 24 weeks, women in the NA group will be
treated with 5 mg NA daily and a placebo injection every 12 weeks. In case of bleeding, the
NA dose will be increased (max 15 mg) until bleeding stops, and then decreased by 2.5 mg
every 4 weeks to a final dose of 7.5 mg which will be maintained for the remainder of the 24
weeks. For the first 24 weeks, women in the GnRH groups will receive Lupron-Depot-3
injections every 12 weeks plus placebo pills daily – bleeding will be treated with an
increase in placebo pills to simulate treatment in the NA group.

After 24 weeks, all women will be on identical regimens of 5 mg NA pills daily and no
injections.

On the first treatment day, subjects will have the following tests/assessments: bone density
with DEXA, scoring of endometriosis symptoms, quality of life questionnaire, general physical
examination, lipid profile, estradiol (E2), N-telopeptide, and pregnancy test. All tests,
except bone density and lipid profile, will be repeated at 12, 24, and 52 weeks of treatment.
Bone density will be performed at 24 and 52 weeks and lipid profile will be performed at 12
and 52 weeks of treatment. In the follow-up period, physical examination, quality of life
questionnaires, scoring of symptoms will be done at 3, 6, 9 and 12 months. Lipid profile,
N-telopeptide and E2 will be performed at 3 and 12 months and bone density at 12 month
follow-up.

The objectives stated above will be compared between the two groups at 12, 24, and 52 weeks
of treatment and at 6-month intervals during the follow-up period.

Overall Status : Recruiting

Start Date : August 2004

Official Title : Phase 3

Phase : Interventional

Study Design : Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Efficacy Study

Enrollment : 112

Verification Date : April 2007

First Received Date : April 9, 2007

Trial Eligibility

Criteria :
Inclusion Criteria:

- The subject has voluntarily signed the Informed Consent form after having the contents
fully explained, after all questions are answered and prior to undergoing any
study-related procedures.

- The subject is a pre-menopausal female at least 18 years of age at the time of
screening having regular periods (21-42 days intervals) with no menopausal
symptoms.

- The subject has a diagnosis of endometriosis made via laparoscopy or laparotomy
(operative report will be obtained) and still symptomatic and at least 3 months after
surgery have a grade 2 and above according to Biberoglu’s pain grade at screening
visit (4 weeks prior initiation of treatment) or 4 out of 10 on a visual pain scale
(visual analogue)

- Subject in good health, except for endometriosis, or has mild medical conditions that
are stable and controlled. The subject has no clinically relevant hepatic, renal,
cardiovascular, respiratory, endocrine, metabolic, psychiatric, neurologic (epilepsy),
hematolytic (coagulopathy) and/or immunologic disease (on steroids) or disorder.

- A subject who has received any of the hormone therapies (GnRH agonist or danazol or
progestin) must meet the minimum washout requirement to be eligible. (GnRH within the
last 6 months and with steroids within the last month.) After hormonal therapy has
stopped, the subject must have returned to normal for at least two menstrual cycles
before baseline time.

- Serum pregnancy and urine qualitative pregnancy tests performed at screening and on
baseline must be negative.

- Unless surgical sterile by bilateral tubal ligation or vasectomy of partner, the
subject agrees to use a double-barrier method of contraception during the screening
period, throughout the 24-week treatment period, such as: condom plus spermicide,
diaphragm plus spermicide, sponge plus spermicide, abstinence is an acceptable form of
birth control.

- Less than grade III overweight or BMI <40 kg/M2

Exclusion Criteria:

- Less than 3 months postpartum and post-lactation at the time of dosing.

- Abnormal laboratory findings considered clinically significant if more than twice the
normal range. Abnormal tests will be repeated, and if still high as stated before,
subject will be excluded.

- A previous history of significant adverse reactions to hormone, progestin or
progesterone and GnRH agonist therapies.

- Abnormal Pap smear in the last 6 months. Subjects with ASCUS (atypical squamous cells
of undetermined significance) and are negative for high-risk human papilloma virus
(HPV) will be eligible. Subjects that have atypical endocervical cells, and atypical
glandular cells are not eligible for this study.

- Subject has a bone density T score less or equal to 2.5, history of nontraumatic
fracture, history of spinal surgery, history of fusion of lumbar region, history of
severe scoliosis greater than 20 degrees.

Gender : Female

Minimum Age : 18 Years

Maximum Age : 55 Years

Healthy Volunteers : No

Facilities

Facility Name : SUNY Downstate Medical Center

Status : Recruiting

City : Brooklyn

State : New York

Zip Code : 11203

Country : United States

Clinical Trial Name -Treatment of Endometriosis With Norethindrone Acetate ( NA) VS. Gonadotropin- Releasing Hormone (GnRH) Agonist (Lupron Depot 11.25 mg)