Open Label Extension Study of PREOS (OLES)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00172133
Recruitment Status : Completed
First Posted : September 15, 2005
Last Update Posted : November 13, 2015
Information provided by (Responsible Party):

Brief 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.

Condition or disease Intervention/treatment Phase
Osteoporosis Drug: ALX1-11 (drug) Phase 3

Shire has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Detailed Description:

Effects of ALX1-11 on bone mineral density (BMD) have been documented in a dose-finding Phase II clinical trial in osteoporotic postmenopausal women, supplemented with calcium and Vitamin D3 but without any other treatment for osteoporosis. The anabolic effects of ALX1-11 in the lumbar vertebrae were statistically significant after the 12-month treatment period and more pronounced than any approved therapy. Additionally, animal studies have shown that the new bone formed by treatment with ALX1 11 is of good quality both histologically and biomechanically.

The primary objective of this OLES 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. A secondary objective is to assess the change in vertebral BMD and compare the changes observed in patients who received ALX1-11 or placebo in Protocol ALX1-11-93001.

Patients will receive 100 µg/day of ALX1-11 daily via subcutaneous injection in this study. Patients should continue the study drug dosing frequency they were following at the end of Protocol ALX1-11-93001.

To enhance their safety, all patients will continue to take their daily supplements of 700 mg calcium and 400 IU Vitamin D3 prior to and during this OLES. Patients whose calcium supplement was discontinued during Protocol ALX1-11-93001 should maintain that discontinuation during this OLES. However upon completion of ALX1-11 dosing in the OLES, oral calcium supplement at a dose of 700 mg each morning should be restarted and maintained for the remainder of the OLES. Additional supplemental calcium and/or Vitamin D3 will not be permitted. A daily multivitamin supplement may be taken during the study. However, the multivitamin must contain no more than 200 mg/day calcium and 400 IU/day Vitamin D3. Patients will be monitored for the development of hypercalcemia and/or hypercalciuria and managed as described in Appendices 4 and 5.

There will be a stopping rule in this OLES. Any patient who reaches a BMD T score of -0.5 or above, at the site or sites (vertebral, total hip, or femoral neck) that were used in the qualification of the patient for Protocol ALX1 11-93001, will stop ALX1-11 treatment. The patient must continue on calcium and Vitamin D3 and be followed for the remainder of this 18-month OLES. At the time of discontinuation, the patient must complete the Month 18 evaluations (Appendix 1A or 1B).

The Clinical Advisory Board (CAB) used in Protocol ALX1-11-93001 will be involved in reviewing any patient issues that arise in this OLES. This group will provide not only continuity of care for all the patients, but also enhanced and consistent safety monitoring for patients participating in the OLES.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1683 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An 18-Month Open Label Extension Study (OLES) of the Safety and Efficacy of Recombinant Human Parathyroid Hormone, rhPTH(1-84), ALX1-11, in Women With Postmenopausal Osteoporosis Who Participated in Protocol ALX1-11-93001 (TOP Study)
Study Start Date : October 2001
Actual Primary Completion Date : April 2005
Actual Study Completion Date : April 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoporosis
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1
All patients entering the study will receive 100mcg daily for up to 6 months, making their total exposure 24 months
Drug: ALX1-11 (drug)
100 mcg PTH(1-84) injected subcutaneously daily in either the thrigh and abdomen.
Other Name: PREOS

Primary Outcome Measures :
  1. 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 (TOP). [ Time Frame: 24 months of treatment ]

Secondary Outcome Measures :
  1. To evaluate the continued efficacy of once-daily treatment with ALX1-11 for maintaining increases in BMD and other measures of bone quality and strength. [ Time Frame: 24 months of treatment ]

Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00172133

  Hide Study Locations
United States, Alabama
'The University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
'Rheumatology Associates of North Alabama
Huntsville, Alabama, United States, 35801
United States, Arizona
'Radiant Research - Phoenix North
Phoenix, Arizona, United States, 85013
United States, California
'Osteoporosis Medical Center
Beverly Hills, California, United States, 90211
'East Bay Clinical Trial Center
Concord, California, United States, 94520
'Loma Linda Osteoporosis Research Center
Loma Linda, California, United States, 92354
Foundation for Osteoporosis Research
Oakland, California, United States, 94612
'Desert Medical Advances
Palm Desert, California, United States, 92260
'VA Palo Alto Health Care System
Palo Alto, California, United States, 94304
'Boling Clinical Trials
Rancho Cucamonga, California, United States, 91730
'S.D. Arthritis & Osteoporosis Medical Clinic
san Diego, California, United States, 92120
'Radiant Research - San Diego
San Diego, California, United States, 92123
'San Francisco General Hospital
San Francisco, California, United States, 94110
United States, Colorado
'Longmont Medical Research Network
Longmont, Colorado, United States, 80501
United States, Connecticut
'Northeast Clinical Research, LLC
Hamden, Connecticut, United States, 06518
United States, Florida
'RASF - Clinical Research Center
Boca Raton, Florida, United States, 33486
'The Center for Diabetes and Endocrine Care
Hollywood, Florida, United States, 33021
'Florida Wellcare Alliance
Inverness, Florida, United States, 34452
'Renstar Medical Group
Ocala, Florida, United States, 34471
'The Arthritis Center
Palm Harbor, Florida, United States, 34684
'The Centre for Arthritis and Rheumatic Diseases
South Miami, Florida, United States, 33143
'Radiant Research - Stuart & LakeWorth
Stuart, Florida, United States, 34996
'Palm Beach Research Center
West Palm Beach, Florida, United States, 33409
United States, Hawaii
'Radiant Research
Honolulu, Hawaii, United States, 96814
United States, Idaho
'Intermountain Orthopaedics
Boise, Idaho, United States, 83702
United States, Illinois
Rush-Prebyterian-St.Luke's Medical Center
Chicago, Illinois, United States, 60612
'The University of Chicago
Chicago, Illinois, United States, 60637
United States, Indiana
'University Hospital & Outpatient Center
Indianapolis, Indiana, United States, 46202
United States, Iowa
'Mercy Arthritis and Osteoporosis Center
Des Moines, Iowa, United States, 50322
United States, Kansas
'Wichita Clinic
Wichita, Kansas, United States, 67208
United States, Louisiana
'Ochsner Clinic
New Orleans, Louisiana, United States, 70121
United States, Maine
'Maine Center for Osteoporosis Research & Education
Bangor, Maine, United States, 04401
United States, Maryland
'Bethesda Health Research Center
Bethesda, Maryland, United States, 20817
'The Osteoporosis and Clinical Trials Center
Cumberland, Maryland, United States, 21502
'Arthritis & Osteoporosis Center of Maryland
Frederick, Maryland, United States, 21702
'The Center for Rheumatology and Bone Research
Wheaton, Maryland, United States, 20902
United States, Massachusetts
'Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Michigan
'Michigan Bone & Mineral Clinic
Detroit, Michigan, United States, 48236
United States, Mississippi
'Desoto Family Medical Center
Olive Branch, Mississippi, United States, 38654
United States, Missouri
'St. John's Medical Research Group
Springfield, Missouri, United States, 65807
United States, New Hampshire
'Arthritis, Osteoporosis Muscle Skeletal Disease Center
Concord, New Hampshire, United States, 03301
United States, New Jersey
'Anderson and Collins Clinical Research Inc.
South Plainfield, New Jersey, United States, 07080
United States, New Mexico
'New Mexico Clinical Research and Osteoporosis Center
Albuquerque, New Mexico, United States, 87106
'Lovelace Scientific Resources
Albuquerque, New Mexico, United States, 87108
United States, New York
'College of Physicians and Surgeons, Columbia University
New York, New York, United States, 10032
'Rochester Clinical Research Inc.
Rochester, New York, United States, 14609
'Stony Brook Clinical Research Trials Center
Stony Brook, New York, United States, 11794
'Physicians Clinical Research Services
White Plains, New York, United States, 10605
United States, North Carolina
'Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, North Dakota
'Odyssey Research Services
Bismarck, North Dakota, United States, 58501
Michael J. Lillestol
Fargo, North Dakota, United States, 58103
'Altru Health Systems / Altru Research Center
Grand Forks, North Dakota, United States, 58201
'Odyssey Research Services
Minot, North Dakota, United States, 58701
United States, Ohio
'Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
'David R. Mandel M.D. Inc.
Mayfield Village, Ohio, United States, 44143
United States, Oklahoma
'Oklahoma Center for Arthritis Therapy & Research, Inc.
Tulsa, Oklahoma, United States, 74114
United States, Oregon
'Osteoporosis Center
Medford, Oregon, United States, 97504
United States, Pennsylvania
'Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635
'Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19131
'University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
'Clinical Research Center of Reading LLP
West Reading, Pennsylvania, United States, 19611
'Radiant Research
Wyomissing, Pennsylvania, United States, 19610
United States, Rhode Island
'Rhode Island Hospital
Providence, Rhode Island, United States, 02903
'Roger Williams Medical Center
Providence, Rhode Island, United States, 02908
United States, South Carolina
'Radiant Research
Anderson, South Carolina, United States, 29621
'Columbia Arthritis Center, PA
Columbia, South Carolina, United States, 29204
'Radiant Research
Greer, South Carolina, United States, 29651
United States, South Dakota
'Rapid City Medical Center
Rapid City, South Dakota, United States, 57701
'Averna Research Institute
Sioux Falls, South Dakota, United States, 57105
'Brown Clinic
Watertown, South Dakota, United States, 57201
United States, Tennessee
Chattanooga, Tennessee, United States, 37404
United States, Texas
'Radiant Research/Dallas
Dallas, Texas, United States, 75235
'Breco Research Inc.
Houston, Texas, United States, 77024
'Diabetes Center of the Southwest
Midland, Texas, United States, 79705
'Diabetes & Glandular Disease Research Associates, P.A.
San Antonio, Texas, United States, 78229
'Radiant Research San Antonio
San Antonio, Texas, United States, 78229
United States, Utah
'Salt Lake Women's Center
Sandy, Utah, United States, 84070
United States, Vermont
'Fletcher Allan Health Center, UHC Campus 1
Burlington, Vermont, United States, 05401
United States, Virginia
'Center for Arthritis and Diabetes
Newport News, Virginia, United States, 23606
'National Clinical Research, Inc.
Richmond, Virginia, United States, 23294
'MCV Physicians Program for Osteoporosis
Richmond, Virginia, United States, 23298
United States, Washington
'Osteoporosis Research Group
Seattle, Washington, United States, 98105
United States, Wisconsin
'University of Wisconsin Medical Foundation
Madison, Wisconsin, United States, 53792
'Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Buenos Aires, BUE, Argentina, C1012AAR
'Centro Médico T.I.E.M.P.O
Buenos Aires, BUE, Argentina, C1117ABH
'Hospital Ramos Mejía
Buenos Aires, BUE, Argentina, C1221ADC
'Centro de Osteopatias Medicas
Capital Federal, CBA, Argentina, C1114AAI
'Universidade Federal do Paraná
Curitiba, PR, Brazil, 80060
'Hospital Santa Casa de Misericórdia do Rio de Janeiro
'Rio de Janeiro, RJ, Brazil, 20020
'Hospital do Servidor Público do Rio de Janeiro
Rio de Janeiro, RJ, Brazil, 20221
'Universidade Federal de São Paulo
Sao Paulo, SP, Brazil, 04038
'Instituto de Saúde e Bem Estar da Mulher
Sao Paulo, SP, Brazil, 04062
'Hospital Heliópolis
Sao Paulo, SP, Brazil, 04231
Canada, Alberta
'Heritage Medical Research Clinic
Calgary, Alberta, Canada, 'T2N 4N1
Canada, British Columbia
Osteoporosis Research Center
Vancouver, British Columbia, Canada, V5Z 2N6
Canada, Manitoba
'Manitoba Clinic
Winnipeg, Manitoba, Canada, 'R3A 1M3
Canada, Ontario
Charlton medical Centre
Hamilton, Ontario, Canada, L8N 1Y2
Rafat Faraawi
Kitchener, Ontario, Canada, N2M 5N6
'Centre for Activity and Aging
London, Ontario, Canada, 'N6G 2M3
St. Joseph's Health Centre
London, Ontario, Canada, N6A 4V2
'Royal Victoria Hospital
Montreal, Ontario, Canada, 'H3A 1A1
Oakville Bone Center
Oakville, Ontario, Canada, L6J 1X8
Ottawa Hospital
Ottawa, Ontario, Canada, 'K1H 8L6
'Sunnybrook and Women's College Health Science Center
Toronto, Ontario, Canada, 'M4N 3M5
'St. Michael's Hospital
Toronto, Ontario, Canada, 'M5C 2T2
'Osteoporosis Research Program
Toronto, Ontario, Canada, 'M5S 1B2
Jude F. Rodrigues
Windsor, Ontario, Canada, N8W 5L7
Canada, Prince Edward Island
'Riverside Medical Centre
Charlottetown, Prince Edward Island, Canada, C1A 6A4
Canada, Quebec
'Complexe Hospitalier de la Sagami
Chicoutimi, Quebec, Canada, G7H 5H6
'Hopital Maisonneuve-Rosemont
Montreal, Quebec, Canada, 'H1T 2M4
'Centre de Recherche du CHUM - Hopital Saint-Luc
Montreal, Quebec, Canada, 'H2X 1P1
Centre de recherche - CORQ
Sainte-Foy, Quebec, Canada, G1V 3M7
Novabyss Research Clinic
Sherbrooke, Quebec, Canada, J1J 2B8
Canada, Saskatchewan
'Saskatoon Osteoporosis Centre
'Saskatoon, Saskatchewan, Canada, 'S7K 0H6
'Soroka Medical Center
Beer Sheva, Israel, 84101
'Rambam Medical Center
Haifa, Israel, 31096
'Lin Medical Center
Haifa, Israel, 34162
'Hadassah University Hospital
Jerusalem, Israel, 91240
'Chaim Sheba Medical Center
Ramat Gan, Israel, 52621
'Lis Maternity Hospital
Tel Aviv, Israel
'Instituto Mexicano de Investigacion Clinica
Mexico, DF, Mexico, 06700
'Hospital de Mexico
Mexico, DF, Mexico, 11800
'Hospital Angeles de las Lomas
'Huixquilucan, Emex, Mexico, 52763
'Hospital Aranda de la Parra
Leon, GTO, Mexico, 37000
'OPD Hospital Civil de Guadalajara Dr. Juan I. Menchaca
Guadalajara, JAL, Mexico, 44340
'Hospital Civil de Belem
Guadalajara, JAL, Mexico, 44650
'Medica Monraz
Guadalajara, JAL, Mexico, 44670
'Hospital Universitario de Monterrey
Monterrey Nuevo Leon, Mexico, 64040
'Spitalul Clinic Judetean Cluj-Napoca
Cluj-Napoca, Romania, 3400
Russian Federation
'Scientific Center of Endocrinology of RAMS
Moscow, Russian Federation, 117036
'Russian Academy for Advanced Medical Studies
Moscow, Russian Federation, 125315
Sponsors and Collaborators
Study Director: Roger Garceau, M.D. NPS Pharma

Responsible Party: Shire Identifier: NCT00172133     History of Changes
Other Study ID Numbers: CL1-11-002
First Posted: September 15, 2005    Key Record Dates
Last Update Posted: November 13, 2015
Last Verified: August 2008

Keywords provided by Shire:
Parathyroid Hormone

Additional relevant MeSH terms:
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases