Osteoporosis
Conditions
Brief summary
A Multi-center study to determine effects of various doses of Macroflux Parathryroid Hormone (PTH) in women with osteoporosis
Interventions
DRUGteriparatide
Macroflux® patch applied to the abdomen for 30 minutes daily
Sponsors
Zosano Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Healthy postmenopausal women age 50 years or older * At least three lumbar vertebrae (L1-L4) must be evaluable by dual energy x-ray absorptiometry (DXA) for bone mineral densitometry that is, without fracture or significant degenerative disease, as determined by the central imaging facility * Have osteoporosis defined as: Either a T-score of ≤ -2.5 at the lumbar spine, femoral neck, or total hip, AND a T-score of at least \< -1.0 at the lumbar spine; or A T-score of ≤ -2.0 at the lumbar spine, femoral neck, or total hip, AND at least one vertebral fracture;
Exclusion criteria
* Active hepatitis; * Active pancreatitis; * Unstable cardiac disease; * Unstable pulmonary disease; * Celiac disease; * Hyper- or hypo-parathyroidism; * Hyperthyroidism; * Cushing's disease; * Osteomalacia; * Paget's disease; * Osteogenesis imperfecta; * Known blood disorders; * History of kidney stones; * Impaired renal function; * Autoimmune diseases; * Bone metastases or a history of skeletal malignancies; * Cancer history that includes any cancer within the previous 5 years, with the exception of squamous or basal cell carcinoma of the skin in which the lesions were fully resected with clear margins described in a written report by a pathologist, and the patient has had no recurrence of lesions for at least 1 year from the time of original resection; * Any condition or disease that may interfere with the ability to have or the evaluation of a DXA scan, for example, severe osteoarthritis of the spine, spinal fusion, pedicle screws, history of vertebroplasty, or degenerative disease that results in insufficient number of evaluable lumbar vertebrae, or \>1 lumbar vertebral fracture in L1-L4; * More than 4 vertebral fractures in T4-L4; * Bilateral hip replacements; * Use of fluoride (e.g. fluoride therapy for osteoporosis) or strontium at any time; * Have received methotrexate or immunomodulatory agents with antiproliferative activity; * With known dermatological disorders that would interfere with the study procedures or assessments, or with a history of contact dermatitis; * With known allergy or sensitivity to tapes, adhesives, PTH, teriparatide or its analogs, or components of the Macroflux® systems; * Who, in the opinion of the investigator, should not participate in the study, or may not be capable of following the study schedule for any reason; and * Unwillingness or inability to abide by the requirements of the study. * Have received any intravenous (IV) administered bisphosphonates in the past 24 months, or \>2 doses of IV administered bisphosphonates total; * Use of oral bisphosphonates before randomization, including investigational bisphosphonates, unless: \<6 months of treatment and off for 6 months, or 6-12 months of treatment and off for 2 years, or \>12 months of treatment and off for 5 years;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Lumbar Spine Bone Mineral Density (BMD): Baseline to Week 24 | 24 weeks | Percent Change in Lumbar Spine Bone Mineral Density (BMD) from Baseline to Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Lumbar Spine Bone Mineral Density: Baseline to Week 12 | 12 weeks | Percent Change in Lumbar Spine Bone Mineral Density from Baseline to Week 12 |
| Absolute Change in Lumbar Spine BMD: Baseline to Week 12 | 12 weeks | Absolute Change in Lumbar Spine BMD from Baseline to Week 12 |
| Percent Change in Total Hip Bone Mineral Density: Baseline to Week 24 | 24 Weeks | Percent Change in Total Hip Bone Mineral Density from Baseline to Week 24 |
| Percent Change in Femoral Neck BMD: Baseline to Week 24 | 24 Weeks | Percent Change in Femoral Neck BMD from Baseline to Week 24 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Macroflux® Placebo Macroflux® placebo patch
teriparatide: Macroflux® patch applied to the abdomen for 30 minutes daily | 33 |
| Macroflux® 20 mcg Macroflux® 20 mcg patch
teriparatide: Macroflux® patch applied to the abdomen for 30 minutes daily | 34 |
| Macroflux® 30 mcg Macroflux® 30 mcg patch
teriparatide: Macroflux® patch applied to the abdomen for 30 minutes daily | 32 |
| Macroflux® 40 mcg Macroflux® 40 mcg patch
teriparatide: Macroflux® patch applied to the abdomen for 30 minutes daily | 33 |
| FORTEO® FORTEO® 20 mcg injection
teriparatide: FORTEO® injection administered subcutaneously (SC) either to the abdomen or thigh | 33 |
| Total | 165 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Macroflux® Placebo | Macroflux® 20 mcg | Macroflux® 30 mcg | Macroflux® 40 mcg | FORTEO® | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 64.8 years STANDARD_DEVIATION 7.1 | 64.1 years STANDARD_DEVIATION 7.5 | 63.6 years STANDARD_DEVIATION 5.8 | 64.6 years STANDARD_DEVIATION 7.3 | 63.2 years STANDARD_DEVIATION 6.8 | 64.06 years STANDARD_DEVIATION 6.9 |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Caucasian | 4 participants | 9 participants | 10 participants | 14 participants | 8 participants | 45 participants |
| Race/Ethnicity, Customized Hispanic | 29 participants | 25 participants | 22 participants | 19 participants | 24 participants | 119 participants |
| Sex: Female, Male Female | 33 Participants | 34 Participants | 32 Participants | 33 Participants | 33 Participants | 165 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 29 / 33 | 32 / 34 | 31 / 32 | 30 / 33 | 23 / 33 |
| serious Total, serious adverse events | 1 / 33 | 1 / 34 | 0 / 32 | 0 / 33 | 0 / 33 |
Outcome results
Primary
Percent Change in Lumbar Spine Bone Mineral Density (BMD): Baseline to Week 24
Percent Change in Lumbar Spine Bone Mineral Density (BMD) from Baseline to Week 24
Time frame: 24 weeks
Population: Intent to treat (ITT)/Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Macroflux® Placebo | Percent Change in Lumbar Spine Bone Mineral Density (BMD): Baseline to Week 24 | -0.33 percent change | Standard Deviation 3.467 |
| Macroflux® 20 mcg | Percent Change in Lumbar Spine Bone Mineral Density (BMD): Baseline to Week 24 | 2.96 percent change | Standard Deviation 3.524 |
| Macroflux® 30 mcg | Percent Change in Lumbar Spine Bone Mineral Density (BMD): Baseline to Week 24 | 3.47 percent change | Standard Deviation 3.575 |
| Macroflux® 40 mcg | Percent Change in Lumbar Spine Bone Mineral Density (BMD): Baseline to Week 24 | 4.97 percent change | Standard Deviation 4.114 |
| FORTEO® | Percent Change in Lumbar Spine Bone Mineral Density (BMD): Baseline to Week 24 | 3.55 percent change | Standard Deviation 3.73 |
Secondary
Absolute Change in Lumbar Spine BMD: Baseline to Week 12
Absolute Change in Lumbar Spine BMD from Baseline to Week 12
Time frame: 12 weeks
Population: ITT/Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Macroflux® Placebo | Absolute Change in Lumbar Spine BMD: Baseline to Week 12 | 0.007 g/cm^2 | Standard Deviation 0.0234 |
| Macroflux® 20 mcg | Absolute Change in Lumbar Spine BMD: Baseline to Week 12 | 0.011 g/cm^2 | Standard Deviation 0.0191 |
| Macroflux® 30 mcg | Absolute Change in Lumbar Spine BMD: Baseline to Week 12 | 0.014 g/cm^2 | Standard Deviation 0.0238 |
| Macroflux® 40 mcg | Absolute Change in Lumbar Spine BMD: Baseline to Week 12 | 0.017 g/cm^2 | Standard Deviation 0.0285 |
| FORTEO® | Absolute Change in Lumbar Spine BMD: Baseline to Week 12 | 0.021 g/cm^2 | Standard Deviation 0.0201 |
Secondary
Percent Change in Femoral Neck BMD: Baseline to Week 24
Percent Change in Femoral Neck BMD from Baseline to Week 24
Time frame: 24 Weeks
Population: ITT/Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Macroflux® Placebo | Percent Change in Femoral Neck BMD: Baseline to Week 24 | 0.172 Percent change | Standard Deviation 3.3432 |
| Macroflux® 20 mcg | Percent Change in Femoral Neck BMD: Baseline to Week 24 | 0.949 Percent change | Standard Deviation 3.2975 |
| Macroflux® 30 mcg | Percent Change in Femoral Neck BMD: Baseline to Week 24 | 0.599 Percent change | Standard Deviation 2.6127 |
| Macroflux® 40 mcg | Percent Change in Femoral Neck BMD: Baseline to Week 24 | 0.750 Percent change | Standard Deviation 2.6132 |
| FORTEO® | Percent Change in Femoral Neck BMD: Baseline to Week 24 | -0.012 Percent change | Standard Deviation 3.66 |
Secondary
Percent Change in Lumbar Spine Bone Mineral Density: Baseline to Week 12
Percent Change in Lumbar Spine Bone Mineral Density from Baseline to Week 12
Time frame: 12 weeks
Population: ITT/Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Macroflux® Placebo | Percent Change in Lumbar Spine Bone Mineral Density: Baseline to Week 12 | 0.97 Percent change | Standard Deviation 3.312 |
| Macroflux® 20 mcg | Percent Change in Lumbar Spine Bone Mineral Density: Baseline to Week 12 | 1.55 Percent change | Standard Deviation 2.606 |
| Macroflux® 30 mcg | Percent Change in Lumbar Spine Bone Mineral Density: Baseline to Week 12 | 2.04 Percent change | Standard Deviation 3.277 |
| Macroflux® 40 mcg | Percent Change in Lumbar Spine Bone Mineral Density: Baseline to Week 12 | 2.5 Percent change | Standard Deviation 2.86 |
| FORTEO® | Percent Change in Lumbar Spine Bone Mineral Density: Baseline to Week 12 | 2.81 Percent change | Standard Deviation 2.771 |
Secondary
Percent Change in Total Hip Bone Mineral Density: Baseline to Week 24
Percent Change in Total Hip Bone Mineral Density from Baseline to Week 24
Time frame: 24 Weeks
Population: ITT/Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Macroflux® Placebo | Percent Change in Total Hip Bone Mineral Density: Baseline to Week 24 | -0.634 Percent change | Standard Deviation 1.9719 |
| Macroflux® 20 mcg | Percent Change in Total Hip Bone Mineral Density: Baseline to Week 24 | 0.138 Percent change | Standard Deviation 2.0386 |
| Macroflux® 30 mcg | Percent Change in Total Hip Bone Mineral Density: Baseline to Week 24 | 0.553 Percent change | Standard Deviation 2.3694 |
| Macroflux® 40 mcg | Percent Change in Total Hip Bone Mineral Density: Baseline to Week 24 | 1.331 Percent change | Standard Deviation 2.1111 |
| FORTEO® | Percent Change in Total Hip Bone Mineral Density: Baseline to Week 24 | 0.094 Percent change | Standard Deviation 2.6194 |