| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Prevention and treatment of osteoporosis. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 6.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10031285 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this study is to compare the effect of orally administered 20 mg arzoxifene daily versus orally administered 60 mg raloxifene daily on 12-month percent change from baseline in lumbar spine BMD in postmenopausal women with osteoporosis, as assessed by dual energy x-ray absorptiometry DXA . |
|
| E.2.2 | Secondary objectives of the trial |
| To compare the effect of treatment with orally administered arzoxifene 20 mg/day versus orally administered raloxifene 60 mg/day on the following data in postmenopausal women with osteoporosis BMD at the femoral neck and total hip, as measured by 6- and 12-month percent change from baseline biochemical markers of bone metabolism, as measured by serum CTX and PINP at baseline, 3, 6, and 12 months coagulation parameters, as measured by Protein C, Protein S, and Antithrombin III at baseline, 3, 6, and 12 months breast density, as assessed from bilateral mammograms performed at screening and 12 months incidence of spontaneous vaginal bleeding, as measured by subject query at each visit overall safety. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
| 1 are ambulatory, 50 to 75 years of age, inclusive. All women must be free of severe or chronically disabling conditions, have a life expectancy of at least 5 years in the opinion of the investigator, be expected to remain ambulatory throughout the entire study, and be expected to return for follow-up visits 2 had their last natural menstrual period at least 2 years before beginning the study 3 are able to comprehend the requirements and procedures for the study and to provide informed consent before entering the study 4 have at least two L1 to L4 lumbar vertebrae that are evaluable via DXA 5 have locally read femoral neck or lumbar spine T-score 61603;-2.5 Table GJAR.1 6 have a follicle stimulating hormone FSH 61502;30 IU/L or 61502;30 mIU/mL |
|
| E.4 | Principal exclusion criteria |
| 7 have known current metabolic bone disorders other than low bone mass,such as hyperparathyroidism,renal osteodystrophy,or osteomalacia 8 have known,suspected,or history of carcinoma of the breast or estrogen-dependent neoplasia e.g.endometrial carcinoma or any ovarian appearance suspicious for malignancy on screening TVU;be disease free and in remission from all other cancers for 5 or more years,except for excised superficial lesions,such as basal cell carcinoma or squamous cell carcinoma of the skin 9 have demonstrated or suspected allergy to raloxifene or arzoxifene or other components of these study medications 10 have unexplained or abnormal vaginal bleeding within 6 months prior to V1 or between V1 and V2 11 are experiencing clinically severe postmenopausal symptoms that may require estrogen-replacement therapy 12 have a history of or suggestion on ultrasound or pelvic examination of a pre-existing gynecologic abnormality that would require further gynecologic treatment e.g.ovarian cysts,large fibroids,undiagnosed adnexal masses 13 have Papanicolaou s tests PAP tests showing malignant or premalignant findings.If the subject has a documented PAP test within 6 months prior to entering the study,and the report demonstrated normal or inflammatory changes only,and this PAP test report is obtained for source documentation,the subject does not need to have the V1 PAP test performed.Abnormal PAP tests must be followed to a benign diagnosis prior to V2 14 for subjects with a uterus, have a screening TVU total bilayer endometrial thickness measurement 5.0 mm,including intracavitary endometrial fluid 15 have any evidence of recent within last 2 years follicular activity consistent with ovulation 16 have active or any past history of thromboembolic events e.g.deep vein-thrombosis,pulmonary embolism,or retinal vein thrombosis 17 have active or any past history of atrial fibrillation 18 have a history of cerebrovascular accident or documented transient ischemic attack at any time in the past 19 have acute or chronic liver disease defined as alanine aminotransaminase ALT 100 U/L,gamma-glutamyl transferase GGT 400 U/L,or late stage cirrhosis without transaminase elevation 20 have impaired kidney function serum creatinine 177 mol/L or 2.0 mg/dL 21 have vit D deficiency,defined as serum 25-hydroxyvitamin D 15 ng/mL or 37.4 nmol/L. If nutritional vit D deficiency is suspected e.g.no malabsorption ,one retest will be allowed.This retest should be performed within 1 week after completing 30 days of calcium and vit D supplementation 22 have any known,severe,or untreated malabsorption syndromes 23 have endocrine disorders requiring pharmacologic therapy except for type II diabetes and hypothyroidism.Subjects on a stable dose of thyroid replacement therapy during the 6 months preceding randomization V2 who are clinically euthyroid in the opinion of the investigator may enroll in the trial 24 consume an excess of alcohol or abuse drugs,in the opinion of the investigator 25 represent an unacceptable medical or psychiatric risk for treatment with an investigational drug,in the opinion of the investigator 26 have active or any history of seizure disorder 27 have breast implants 28 have received treatment with any of the medications listed in Table GJAR.2,according to the listed Conditions for Exclusion,in each case 29 have received treatment within the last 30 days with a drug,not including study drug,that has not received regulatory approval for any indication at the time of study entry 30 are investigator site personnel directly affiliated with this study and/or their immediate families spouse,parent,child or sibling,whether biological or legally adopted 31 are Lilly employees or are involved in any way with the development of arzoxifen 32 have previously entered or enrolled in this study or have completed or withdrawn from any other study investigating arzoxifene or have withdrawn from a previous raloxifene study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Posterior-anterior lumbar spine BMD measurement. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
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