Open Label Extension Study of PREOS

• Status: Completed
• Trial end date: 2005-04-13
• Target enrollment: 0
• Participant gender: Female

Summary

This is an Open Label Extension Study (OLES) for patients who participated in the 18 month double-blind, placebo-controlled, Phase III trial (Protocol ALX1 11 93001 the TOP Study) studying the effect of ALX1-11, recombinant human parathyroid hormone, rhPTH(1-84), on vertebral fracture incidence. The primary objective of this study is to evaluate the safety of continued dosing with ALX1-11, up to a maximum of 24 months, in postmenopausal osteoporotic women who participated in Protocol ALX1 11 93001.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shire

Criteria

Inclusion Criteria:

• Women who completed 18 months of treatment in Protocol ALX1-11-93001; or

• Women prematurely discontinued from Protocol ALX1-11-93001 who want to participate in OLES for the events listed below must have their clinical course reviewed and approved by the CAB for enrollment into the OLES:

• Clinical or incident lumbar vertebral fractures as assessed by the central imaging organization

• Clinical or incident hip fracture

• Confirmed bone loss at A/P lumbar vertebra or total hip or femoral neck as assessed by the central imaging organization

• Body weight below 40 kg

• Development of an exclusion criterion in Protocol ALX1-11-93001

• It must be accepted by patients whose clinical courses are reviewed by the CAB that participation in OLES may require additional tests at baseline and/or during the study to ensure their utmost safety.

• Women with the ability to self-administer a daily injection or have a designee who will give the injections;

• Women who are capable of understanding and giving written, voluntary informed consent before the start of open-label dosing with ALX1-11.

Exclusion Criteria:

A. History or Concurrent Illness:

Disorders of Immunity Endocrine system Gastrointestinal system Kidney and collecting system Liver, biliary tract and pancreatic systems Musculoskeletal system

• Patients with chronic, active joint disease requiring more than one intra-articular injection every 6 months Neoplasia

• Patients who have had squamous or basal cell carcinoma of the skin may enter this study if:

1. The lesion(s) were fully resected with clear margins described in a written report by a pathologist, and

2. The patient has had no recurrence of lesions for at least one year from the time of the original resection.

Nervous system Vascular, respiratory and cardiac system *Significant diseases or disorders are determined by history, physical exam or laboratory tests and judged by the Principal Investigator to be significant.

B. Concurrent Medication:

Patients may not use any of the following therapies while they are enrolled in this OLES without permission from the Sponsor and the PMO:

• Tetracycline antibiotics for four weeks prior to bone biopsy

• Any PTH analogs [e.g., rhPTH(1-84), PTH(1-34), PTHrP and analogs]

• Fluoride

• Strontium

• Phenytoin for seizure control

• Any investigational drug other than ALX1-11

• Anabolic steroids or androgens

• Active Vitamin D3 metabolites and analogs, e.g., calcitriol

• Systemic corticosteroids, more than 5 mg/day prednisone or a systemic corticosteroid formulation equivalent to 5 mg/day prednisone

1. A patient who has been enrolled into the OLES and needs to receive an acute bolus of steroids (oral or injectable) for a self-limited illness may continue treatment in the study if the following requirements are met:

1. Exposure to steroids will be limited to no more than 30 consecutive days

2. The maximal dose of steroid (prednisone equivalent) must be limited to no more than 225 mg (7.5 mg each day for 30 days)

3. The illness is acute in nature and is not expected to recur during the remaining period of the study

• Bisphosphonates, including investigational bisphosphonates

• Calcitonin

• Estrogen replacement therapy by oral, transdermal or intramuscular administration

• SERM drugs, e.g., tamoxifen, raloxifene, Evista

• Vaginal application of estrogen-containing creams unless the dose is:

1. conjugated estrogen or estradiol: maximum of 0.5 g twice each week (total of 1.0 g weekly)

2. Estrace (Ogen): maximum of 1.0 g twice each week (total of 2.0 g weekly)

• Daily inhaled corticosteroid unless dose is equivalent to <1200 µg/day of beclomethasone

• Cytostatics, e.g., azathioprine, recombinant human tumor necrosis fusion (Fc) protein, monoclonal antibody against tumor necrosis factor (e.g., remicade [infliximab]

• Methotrexate

1. The antimetabolite, methotrexate, which interferes with DNA synthesis, repair and cellular replication should not be used by patients participating in this OLES.

• In general, immunomodulatory agents with antiproliferative activity are not permitted as a concomitant medication in this OLES.

• Intra-articular injections

1. Patients may receive a maximum of one intra-articular injection (ONE JOINT ONLY) every 6 months while participating in this OLES. The joint that is injected may be a different joint every 6 months. The dose of corticosteroid injected should not exceed the anti-inflammatory equivalent dose of Prednisone 40 mg suspension. The dose and volume should be adjusted downward as appropriate to the size of the joint.

• Provera is an acceptable concomitant medication when used according to the label instructions

Patients may be enrolled in this OLES if they have been stabilized on the following therapy for the specified amount of time:

• Thyroid Hormone (<0.1 mg/day thyroxine) therapy for at least 6 months If taking > 0.1 mg/day but < 0.2 mg/day, must have serum TSH level 1. > 0.1mU/L. Patients will be excluded if they are taking doses of > 0.2 mg/day.

2. However, if a patient has had a minimal change in L-thyroxine dose of < 0.025 mg/day within 6 months of the baseline visit, and has been on this new dose for at least 2 months, the patient may be enrolled in this study. The patient's history with L-thyroxine must be clearly documented in the source documents.

3. If a patient requires an increase in their thyroid replacement dose, as recommended by a physician who is caring for the patient, after enrollment in this OLES, the patient must have a TSH and T4 level within 3 months of the dose change to ensure the patient does not become hyperthyroid

• Stable dosage of thiazide for at least 3 consecutive months

C. Laboratory Values and Physical Examination Findings:

• Serum calcium greater than 10.7 mg/dL (2.66 mmol/L) at baseline will be managed as outlined in Appendix 4

• Urinary calcium to creatinine ratio greater than or equal to 1 at baseline will be managed as outlined in Appendix 5

• Elevated total serum alkaline phosphates (> 400 U/L) at baseline will be managed as outlined in Appendix 6 except as noted for Latin and South American countries.

• Any other clinically significant abnormal value as judged by the investigator

D. Substance Abuse:

Alcohol and/or drug abuse

E. Compliance:

Suspected or confirmed poor compliance in completing clinical trial evaluations and/or clinical trial required questionnaires