Clinical trial NCT00511342: Effects on Bone Mineral Density (BMD) of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing LNG/EE (292005)(P05765)(COMPLETED)
Official title: An Open-Label, Randomized, Single Center Trial in Healthy Young Women, to Evaluate the Effects of a Monophasic Combined Oral Contraceptive (COC) Containing 2.5 mg NOMAC and 1.5 mg E2 on Bone Mineral Density (BMD) Compared to a Monophasic COC Containing 0.150 mg Levonorgestrel and 0.030 mg Ethinyl Estradiol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Contraception
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2007-08-03
Enrollment: 110
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary purpose of this study is to evaluate the effects of the NOMAC-E2 combined oral contraceptive (COC) on bone mineral density (BMD).


Eligibility criteria: Inclusion criteria:

* Sexually active women, at risk for pregnancy and not planning to use condoms

during treatment;

* At least 20 but not older than 35 years of age at the time of screening;
* BMI = 17 and = 35;
* Good physical and mental health;
* Willing to give informed consent in writing;
* Willing to take part in the trial for two years.

Exclusion criteria:

* Family history of osteoporotic fracture below the age of 70;
* Postgastrectomy;
* History of eating disorder, viz. anorexia nervosa, bulimia;
* Endocrine disorder (including controlled diabetes, \[para\]thyroid disease, Cushing's disease);
* Rheumatoid arthritis;
* Significant scoliosis;
* Fasting parathyroid hormone (PTH) outside the reference range at screening;
* Fasting calcitonin outside the reference range at screening;
* Prolactin above the reference range (hyperprolactinemia) at screening;
* Fasting cholesterol and/or triglycerides above the reference range for age at screening (treatment with lipid lowering drugs not allowed);
* Engaging in vigorous exercise such as marathon, competitive swimming, triathlon;
* Smoking more than ten cigarettes/day;
* Use of more than two units of alcohol a day;
* Use of one or more of the following drugs:

  * gonadotropin releasing hormone (GnRH) analogues (also past use for more than six months at any time, or for any period of time less than six months ago is a contraindication);
  * systemic or inhaled administration of corticosteroids (also past use for more than one year, less than five years ago or any period of time in the past year is a contraindication);
  * thiazide diuretics;
  * thyroid hormone;
  * bisphosphonates;
  * calcium supplementation in combination with vitamin D supplementation/

calcitonin;

* ever treatment after childhood with fluorides;

  * Contraindications for contraceptive steroids
  * An abnormal cervical smear (i.e.: dysplasia, cervical intraepithelial neoplasia\[CIN\], squamous intraepithelial lesion \[SIL\], carcinoma in situ, invasive carcinoma) at screening;
  * Clinically relevant abnormal laboratory result at screening as judged by the investigator;
  * Use of an injectable hormonal method of contraception; within 6 months of an injection with a 3-month duration, within 4 months of an injection with a 2-month duration, within 2 months of an injection with a 1-month duration;
  * Within 12 months after a pregnancy prior to the start of trial medication;
  * Breastfeeding or within 12 months after stopping breastfeeding prior to the start of trial medication;
  * Present use or use within 2 months prior to the start of the trial medication of the following drugs: phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, ketoconazole, sex steroids (other than pre- and post-treatment contraceptive method) and herbal remedies containing Hypericum perforatum (St John's Wort);
  * Administration of investigational drugs and/or participation in another clinical trial within 2 months prior to the start of the trial medication or during the trial period.

Primary outcomes:
measure: Mean Change From Baseline in Z-scores of the Lumbar Spine (L2-L4) and Femoral Neck
timeFrame: Baseline and after cycle 26 (2 years)
Secondary outcomes:
measure: Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
timeFrame: 2 years (26 cycles)
measure: Number of Participants With an Occurrence of Breakthrough Bleeding/ Spotting
timeFrame: Every 28-day cycle for 26 cycles (2 years total)
measure: Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
timeFrame: Every 28-day cycle for 26 cycles (2 years total)
measure: Number of Participants With an Occurrence of Breakthrough Bleeding
timeFrame: Every 28-day cycle for 26 cycles (2 years total)
measure: Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
timeFrame: Every 28-day cycle for 26 cycles (2 years total)
measure: Number of Participants With an Occurrence of Early Withdrawal Bleeding
timeFrame: Every 28-day cycle for 26 cycles (2 years total)
measure: Number of Participants With an Occurrence of Continued Withdrawal Bleeding
timeFrame: Every 28-day cycle for 26 cycles (2 years total) including one week after stopping treatment
measure: Average Number of Breakthrough Bleeding-Spotting Days
timeFrame: Every 28-day cycle for 26 cycles (2 years total)
measure: Average Number of Withdrawal Bleeding-spotting Days
timeFrame: Every 28-day cycle for 26 cycles (2 years total)
Other outcomes:
Locations:
Study officials:
References:
citation: Sordal T, Grob P, Verhoeven C. Effects on bone mineral density of a monophasic combined oral contraceptive containing nomegestrol acetate/17beta-estradiol in comparison to levonorgestrel/ethinylestradiol. Acta Obstet Gynecol Scand. 2012 Nov;91(11):1279-85. doi: 10.1111/j.1600-0412.2012.01498.x. Epub 2012 Aug 21.