A Study to Assess the Safety and Efficacy of 3 Doses of ALX1-11 (50, 75, and 100µg) in the Treatment of Postmenopausal Osteoporosis

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: NCT00172107
Recruitment Status : Completed
First Posted : September 15, 2005
Last Update Posted : November 13, 2015
Information provided by (Responsible Party):

Brief Summary:
A double-blind, placebo-controlled, parallel-group study to assess the safety and efficacy of 3 doses of ALX1-11 (recombinant human parathyroid hormone [rhPTH(1-84)])(50, 75 and 100 µg) in the treatment of postmenopausal osteoporosis. The primary objective of this study is to compare the efficacy of ALX1-11 (50, 75 and 100 µg) with that of placebo in terms of increasing vertebral bone mineral density, when given daily by subcutaneous injection for 12 months in postmenopausal women with osteoporosis.

Condition or disease Intervention/treatment Phase
Osteoporosis Drug: ALX1-11 50 mcg Drug: placebo Drug: ALX1-11 75mcg Drug: ALX1-11 Phase 2

Detailed Description:

Human clinical experience with a synthetic human parathyroid hormone fragment (rhPTH 1-34) and animal studies with ALX1-11 demonstrate consistent increases in bone mineral density. Furthermore, the newly formed bone is normal in structure and composition. Therefore, ALX1-11 (recombinant human parathyroid hormone [rhPTH 1-84]) has the potential to stimulate new bone formation in osteoporotic patients thereby increasing trabecular bone density and preventing fractures. The clinical profile for ALX1-11 can be expected to be unique, since none of the approved therapies for osteoporosis are able to form the quantities of new bone that ALX1-11 is potentially capable of. Patients with bone density below the "fracture threshold" (osteopenia), as well as those with established vertebral fractures (osteoporosis), would be expected to benefit from treatment.

Animal toxicology studies have been completed and there were no results to indicate any restrictions in the clinical usage of the drug. Preliminary human clinical experience with ALX1-11 in healthy, postmenopausal females has demonstrated no apparent risk of frank hypercalcemia* at single administrations up to 5.0 µg/kg or daily administrations for 7 days up to 2.0 µg/kg/day.

Based on these studies, the anticipated therapeutic range of ALX1-11 is 50-100 µg per day (approx. 1.0 - 1.5 µg/kg/day). Therefore, the dose range to be tested in this study will include an anticipated minimally effective dose, interim dose and maximally tolerable dose (50, 75 and 100 µg). The efficacy of 3 doses of ALX1-11 will be assessed in terms of bone mineral density and biochemical markers of bone turnover in postmenopausal women.

The primary objective of this study is to determine the dose-response relationship of ALX1-11 in terms of bone mineral density. The efficacy of the 3 doses of ALX1-11 relative to placebo will be determined by measurement of bone mineral density (by DXA) at baseline and at 3, 6 and 12 months.

Patients will administer a daily subcutaneous injection of 0.5 mL of either 50, 75 or 100 µg of ALX1-11 or placebo every morning for 12 months.

Women will be advised to use the provided calcium supplements (500mg elemental calcium) to maintain a total daily intake of 1000-1500 mg/day and vitamin D supplements will also be provided (400 IU/day). A dietary questionnaire will be done at visit screen, 6 and 15.

If a patient's total serum calcium measurement, during the treatment phase, demonstrates frank hypercalcemia OR if her pre-dose calcium levels are more than 0.5 mg/dL or 0.125 mmol/L above the upper limit of normal (2.78 mmol/L or 11.1 mg/dL), then the patient's serum calcium level must be repeated.

If upon re-test a patient continues to demonstrate frank hypercalcemia OR if her basal pre-dose calcium levels continues to be elevated above the upper limit of normal, then the patient will be withdrawn from the study.

*Frank Hypercalcemia: defined as total serum calcium levels above 11.1 mg/dL or 2.78 mmol/L

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 217 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Double Blind, Placebo Controlled, Parallel-Group Study to Assess the Safety and Efficacy of 3 Doses of ALX1-11 (50, 75, and 100µg) in the Treatment of Postmenopausal Osteoporosis
Study Start Date : May 1995
Actual Primary Completion Date : March 1997
Actual Study Completion Date : March 1997

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoporosis

Arm Intervention/treatment
Placebo Comparator: 1
Placebo drug injectable subcutaneously
Drug: placebo
placebo powder for subcutaneous injection

Experimental: 2
50 mcg PTH(1-84)
Drug: ALX1-11 50 mcg
PTH(1-84) 50 mcg for subcutaneous injection into thigh or abdomen
Other Name: PREOS

Experimental: 3
75mcg PTH(1-84)
Drug: ALX1-11 75mcg
PTH(1-84)75 mcg for subcutaneous injection
Other Name: PREOS

Experimental: 4
100 mcg PTH(1-84)
Drug: ALX1-11
PTH (1-84) 100mcg for subcutaneous injection into thigh or abdomen
Other Name: PREOS

Primary Outcome Measures :
  1. Efficacy was assessed as percent change from baseline in BMD, BMC, and BMA at the lumbar spine, total hip, femoral neck and whole body (excluding the head) using DXA. [ Time Frame: 12 months of treatment ]

Secondary Outcome Measures :
  1. Secondary efficacy evaluations were also performed at Month 3, 6, and 12: Percent change from baseline in lumbar spine BMC and BMA; Percent change from baseline in total hip and femoral neck BMD, BMC and BMA [ Time Frame: 12 months ]

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Ages Eligible for Study:   50 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Post-menopausal women aged 50-75 years at Visit 1 (at least 5 years post cessation of menses, or FSH>20 IU/L, serum estradiol <110 pmol/L)
  • Vertebral bone mineral density at least 2.5 S.D. below the mean of young normals. Patients must have at least 2 measurable contiguous vertebral bodies in the lumbar region, L1-L4.
  • Ability to self administer injections
  • Ability and willingness to give informed consent

Exclusion Criteria:

  • Evidence of 5 or more vertebral fractures
  • Evidence of 2 or more vertebral fractures in the region L1-L4
  • Presence of significant cardiac disease as determined by history, physical examination and laboratory screens e.g. cardiac dysrhythmias.
  • Presence of significant hepatic, renal, pulmonary, gastrointestinal, hematological, endocrine, immunologic, neurological or psychiatric disease as determined by history, physical examination and laboratory screens. Specifically excluded are diseases known to contribute to osteoporosis: hyperparathyroidism, hyperthyroidism, glucocorticoid excess, hyper or hypocalcemia, Paget's disease, osteogenesis imperfecta, osteomalacia and severe scoliosis.
  • Evidence of lumbar fusions, osteophytes or excessive degenerative disease which precludes reasonable DXA measurement.
  • History or presence of cancer within the previous 5 years except for superficial basal cell and squamous cell carcinomas of the skin.
  • Treatment with any of the following therapies:

    • Any form of Estrogen within previous 6 months
    • Prior use of Etidronate for more that 2 treatment cycles (2weeks/cycle) and/or any use within prior 6 months
    • Any other bisphosphonate
    • Parathyroid Hormone use within 6 months
    • Fluoride (>10 mg/day) within 12 months
    • Any form of Calcitonin within previous 4 months
    • Thyroid hormone within previous 4 months unless TSH levels found to remain within normal range
    • Other therapies known to influence bone metabolism* within previous 4 months
    • Any investigational compound within previous 3 months
    • Abnormal serum Ca++ level: patients having two (2) consecutive serum calcium above 2.66 mmol/L (10.6 mg/dl) will be excluded.
    • History of positive test for Hepatitis B or C, or urine drug screen.
    • History of alcohol or drug abuse: an excess of alcohol is defined as more than 4 or any combination of more than four (4) of the following per day: 120 mL wine, 360 mL beer or wine cooler or 30 mL whiskey.
    • Weight more than 25% above ideal body weight, (minimum 45 kg) as listed in the Metropolitan Life Insurance Tables (Appendix 3)
    • Deemed unsuitable, in the opinion of the investigator, for any other reason.

(*Chronic or continued use of medication that may affect bone calcium metabolism, e.g. thiazide diuretics, oral or injectable steroids, antimitotics (methotrexate), heparin, anticonvulsants and supplements of Vitamin D in excess of 1,000 IU per day and Vitamin A in excess of 10,000 IU per day)

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): NCT00172107

United States, Arizona
Pivotal Research
Peoria, Arizona, United States, 85381
United States, California
Loma Linda Osteoporosis Research Clinic
Loma Linda, California, United States, 92354
Steven Harris
Mill Valley, California, United States, 94941
John Wayne Cancer Institute
Santa Monica, California, United States, 90404
United States, Colorado
Paul Miller
Lakewood, Colorado, United States, 80227
Longmont Medical Research Network
Longmont, Colorado, United States, 80501
United States, Florida
Radiant Research, Stuart
Stuart, Florida, United States, 34996
United States, Maine
Maine Center for Osteoporosis Research and Education of St. Joseph's Hospital
Bangor, Maine, United States, 04401
United States, Maryland
'Bethesda Health Research Center
Bethesda, Maryland, United States, 20817
United States, New York
Helen Hayes Hospital
West haverstraw, New York, United States, 10993
United States, Oregon
Oregon Osteoporosis Center
Portland, Oregon, United States, 97213
United States, Texas
Simona Scumpia
Austin, Texas, United States, 78758
Radiant Research, Dallas
Dallas, Texas, United States, 75235
'Diabetes & Glandular Disease Research Associates, P.A.
San Antonio, Texas, United States, 78229
United States, Washington
Northwest Lipid Research Center
Seattle, Washington, United States, 98104
Canada, Alberta
Heritage Medical Research Clinic
Calgary, Alberta, Canada, T2N 4N1
Canada, British Columbia
Osteoporosis Research Center
Vancouver, British Columbia, Canada, V5Z 2N6
Canada, Nova Scotia
Capital Health Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
St. Joseph's Health Center
London, Ontario, Canada, N6A 4V2
Sponsors and Collaborators
Principal Investigator: Robert Lindsay, M.D. Helen Hayes Hospital, West Haverstraw, NY

Responsible Party: Shire Identifier: NCT00172107     History of Changes
Other Study ID Numbers: CL1-11-821
First Posted: September 15, 2005    Key Record Dates
Last Update Posted: November 13, 2015
Last Verified: September 2005

Keywords provided by Shire:
Parathyroid Hormone

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