OsteoporosisPhase 2NCT00172107
A Study to Assess the Safety and Efficacy of 3 Doses of ALX1-11 (50, 75, and 100µg) in the Treatment of Postmenopausal Osteoporosis
A Phase 2 study testing ALX1-11 50 mcg, ALX1-11 75mcg and ALX1-11 in people with Osteoporosis, run by Shire at 19 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 75 years, women only
- Conditions the study is for
- Osteoporosis
- What is being tested?
- ALX1-11 50 mcg, ALX1-11 75mcg and ALX1-11
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 217 participants
- Where
- 19 sitesin 2 countries
- Study dates
- 18 May 1995to 24 Mar 1997
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 22Show fewer
- 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)
Trial locations and contacts
19 sites in 2 countries.
19 sites in 2 countries
United States15 sites
Simona Scumpia
Austin, Texas, 78758
Maine Center for Osteoporosis Research and Education of St. Joseph's Hospital
Bangor, Maine, 04401
'Bethesda Health Research Center
Bethesda, Maryland, 20817
Radiant Research, Dallas
Dallas, Texas, 75235
Paul Miller
Lakewood, Colorado, 80227
Loma Linda Osteoporosis Research Clinic
Loma Linda, California, 92354
Longmont Medical Research Network
Longmont, Colorado, 80501
Steven Harris
Mill Valley, California, 94941
Pivotal Research
Peoria, Arizona, 85381
Oregon Osteoporosis Center
Portland, Oregon, 97213
'Diabetes & Glandular Disease Research Associates, P.A.
San Antonio, Texas, 78229
John Wayne Cancer Institute
Santa Monica, California, 90404
Northwest Lipid Research Center
Seattle, Washington, 98104
Radiant Research, Stuart
Stuart, Florida, 34996
Helen Hayes Hospital
West Haverstraw, New York, 10993
Canada4 sites
Heritage Medical Research Clinic
Calgary, Alberta, T2N 4N1
Capital Health Centre
Halifax, Nova Scotia, B3H 1V7
St. Joseph's Health Center
London, Ontario, N6A 4V2
Osteoporosis Research Center
Vancouver, British Columbia, V5Z 2N6
About this study
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
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.
Read the 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
- Conditions
- Osteoporosis
- Being tested
- ALX1-11 50 mcg, placebo, ALX1-11 75mcg, ALX1-11
- Keywords
- Post-menopausal, Osteoporosis, Parathyroid Hormone, PTH, ALX1-11
- Medical subject headings
- Osteoporosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALX1-11 50 mcgDrug
Also called PREOS
PTH(1-84) 50 mcg for subcutaneous injection into thigh or abdomen
placeboDrug
placebo powder for subcutaneous injection
ALX1-11 75mcgDrug
Also called PREOS
PTH(1-84)75 mcg for subcutaneous injection
ALX1-11Drug
Also called PREOS
PTH (1-84) 100mcg for subcutaneous injection into thigh or abdomen
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Placebo drug injectable subcutaneously Receives: Drug: placebo |
| 2 | Experimental | 50 mcg PTH(1-84) Receives: Drug: ALX1-11 50 mcg |
| 3 | Experimental | 75mcg PTH(1-84) Receives: Drug: ALX1-11 75mcg |
| 4 | Experimental | 100 mcg PTH(1-84) Receives: Drug: ALX1-11 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months of treatment
Secondary outcomes (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
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study start18 May 1995
- Primary completion24 Mar 1997
- Study completion24 Mar 1997
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 217 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00172107
- Sponsor's protocol ID
- CL1-11-821
- Status last verified
- May 2021
- First submitted
- 12 Sep 2005
- Last updated
- 17 May 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00172107
- Acronym / sponsor ID
- CL1-11-821
- Conditions
- Osteoporosis
- Keywords
- Post-menopausal, Osteoporosis, Parathyroid Hormone, PTH, ALX1-11
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 217 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 18 May 1995 (actual)
- Primary completion
- 24 Mar 1997 (actual)
- Study completion
- 24 Mar 1997 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Drug: placeboPlacebo drug injectable subcutaneously |
| 2 | Experimental | Drug: ALX1-11 50 mcg50 mcg PTH(1-84) |
| 3 | Experimental | Drug: ALX1-11 75mcg75mcg PTH(1-84) |
| 4 | Experimental | Drug: ALX1-11100 mcg PTH(1-84) |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALX1-11 50 mcgAlso: PREOSPTH(1-84) 50 mcg for subcutaneous injection into thigh or abdomen | Drug | 2 |
| placeboplacebo powder for subcutaneous injection | Drug | 1 |
| ALX1-11 75mcgAlso: PREOSPTH(1-84)75 mcg for subcutaneous injection | Drug | 3 |
| ALX1-11Also: PREOSPTH (1-84) 100mcg for subcutaneous injection into thigh or abdomen | Drug | 4 |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
19 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ALX1-11 50 mcg, ALX1-11 75mcg and ALX1-11 in people with Osteoporosis, run by Shire at 19 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2021.