Combination Therapy for Osteoporosis in Men

(Osteo-Men Trial)

Overseen By Anne L Schafer, MD

Age: 18+

Sex: Male

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must be taking: Teriparatide

Must not be taking: Bisphosphonates, Denosumab, Antidepressants, others

Disqualifiers: Metabolic bone disease, Cancer, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 11

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for osteoporosis in men by testing a combination of two drugs: teriparatide (a form of human parathyroid hormone) and cinacalcet. The goal is to determine if this combination can improve bone density and strength more effectively than teriparatide alone. Men with low bone mass who have experienced bone-related issues, such as fractures, or have a family history of such problems might be suitable for this study. Participants will receive daily doses of these medications for 11 months to assess changes in their bone health. As a Phase 4 trial, this research aims to understand how this already FDA-approved and effective treatment can benefit more patients.

Do I need to stop my current medications to join the trial?

Yes, you may need to stop certain medications. The trial excludes participants who have used osteoporosis drugs like bisphosphonates, denosumab, or teriparatide within specific time frames before joining. Additionally, drugs affecting calcium levels or metabolized through certain liver enzymes are also restricted.

What is the safety track record for these treatments?

Research shows that teriparatide is generally safe and well-tolerated. This approved medication helps build bone mass, though some individuals might experience side effects like increased calcium levels. Studies indicate that teriparatide strengthens bones and improves their structure.

The researchers are exploring the combination of teriparatide with another drug, cinacalcet, for additional benefits. Cinacalcet activates calcium receptors, aiding in new bone formation. Although this combination is relatively new, teriparatide itself has a strong safety record.

Since this trial is in a later stage, teriparatide and cinacalcet have been tested in people before. This suggests they are likely safe, but the study will still carefully monitor participants for any side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for osteoporosis in men because they combine teriparatide, a form of human parathyroid hormone, with either a calcimimetic agent called cinacalcet or a placebo, to explore new ways to strengthen bones. Unlike traditional treatments like bisphosphonates, which mainly work by slowing bone loss, teriparatide actively stimulates new bone formation, offering a different approach to managing osteoporosis. The combination with cinacalcet is particularly intriguing, as it may enhance the bone-building effects of teriparatide by modulating calcium levels in the body. This innovative pairing could potentially offer a more robust solution for improving bone density and reducing fracture risk in men with osteoporosis.

What evidence suggests that this trial's combination therapy could be effective for osteoporosis in men?

Research has shown that teriparatide, also known as PTH (1-34), effectively increases bone strength in men with osteoporosis. It encourages the growth of new bone cells, strengthening bones and reducing fracture risk. In animal studies, combining teriparatide with a drug like cinacalcet, which affects calcium levels, improved bone strength and density even further. In this trial, one group of participants will receive teriparatide and cinacalcet, while another group will receive teriparatide with a placebo. This combination targets two different areas involved in bone growth, potentially leading to better results than using teriparatide alone. The combination is now being tested to determine its effectiveness in helping men with low bone mass. ^{6 7 8 9 10}

Who Is on the Research Team?

Dolores M Shoback, MD

Principal Investigator

San Francisco VA Medical Center, San Francisco, CA

Are You a Good Fit for This Trial?

Men with osteoporosis can join this trial if they have a low bone mass score at certain sites in their body or additional risk factors for fractures. They must not have other metabolic bone diseases, severe heart issues, very high or low vitamin D levels, poorly controlled diabetes, recent cancer (except some skin cancers), and should not be on certain medications like steroids or drugs affecting calcium levels.

Inclusion Criteria

You need to have reliable bone density measurements at least two levels in your lower spine.

My bone density is low, indicating osteoporosis or I have a slightly higher bone density but with another risk factor for bone fractures.

Exclusion Criteria

I haven't taken osteoporosis drugs, including specific treatments, in specified time frames.

I have taken oral steroids equivalent to 5 mg of prednisone or more in the last 3 months.

I have changed my testosterone therapy dose or had androgen deprivation therapy in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Run-in

Participants take only calcium and vitamin D supplements to stabilize baseline conditions

4 weeks

1 visit (in-person)

Treatment

Participants receive daily subcutaneous injections of TPTD and either cinacalcet or placebo for 11 months

48 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cinacalcet
• Teriparatide or human parathyroid hormone (PTH) 1-34

Trial Overview The study is testing whether a combination of two drugs—Teriparatide (TPTD) and Cinacalcet—is more effective than TPTD alone in increasing bone density and strength in men with osteoporosis. Participants will receive either the drug combo or TPTD with a placebo for 11 months to compare effects on spine and hip bone density as well as blood markers of bone metabolism.

How Is the Trial Designed?

Group I: teriparatide (TPTD) + the calcimimetic cinacalcet Experimental Treatment 4 Interventions

Combination arm: Men randomized to this arm will take daily subcutaneous injections of teriparatide \[PTH (1-34)\] (20 mcg per day) and at the same time swallow a 30-mg tablet of cinacalcet. Men in both arms of the study will take a total of approximately 1000 mg elemental Ca through their diets and study provided Ca supplements (Ca citrate) and approximately 1000 IU vitamin D3. Men will be followed and assessed throughout the entire study using the clinical (vital signs, adverse events), laboratory (blood and urine tests) and densitometric procedures (DXA BMD and TBS) outlined in the study protocol.

Group II: teriparatide (TPTD) + placebo Placebo Group 4 Interventions

Monotherapy arm: Men randomized to this arm will take daily subcutaneous injections of teriparatide \[PTH (1-34)\] (20 mcg per day) and at the same time swallow a placebo tablet. Men in both arms of the study will take a total of approximately 1000 mg elemental Ca through their diets and study provided Ca supplements (Ca citrate) and approximately 1000 IU vitamin D3. Men will be followed and assessed throughout the entire study using the clinical (vital signs, adverse events), laboratory (blood and urine tests) and densitometric procedures (DXA BMD and TBS) outlined in the study protocol.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

Teriparatide, a treatment for postmenopausal osteoporosis and osteoporosis in men, has been used for over 5 years, providing substantial data on its long-term safety, particularly regarding its registered dose of 20 microg/day.

While teriparatide is effective, there are important safety considerations, including the potential for hypercalcemia, hypercalciuria, and hyperuricemia, as well as a 'black-box' warning from the FDA about the risk of osteogenic sarcoma observed in rat studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of parathyroid hormone for the treatment of osteoporosis. Miller, PD.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/12510800/

The effect of teriparatide [human parathyroid hormone (1- ... This study shows that teriparatide treatment results in an increase in bone mineral density and is a potentially useful therapy for osteoporosis in men.

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT03994172

Novel Combination Therapy for Osteoporosis in Men This trial will test a novel combination therapy for osteoporosis in men based on exciting laboratory findings in mice. TPTD works to raise bone mass and ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2405525523000705

Teriparatide and etelcalcetide improve bone, fibrosis, and ... In CKD model rats, the combination of EC and TPTD was more effective in increasing cortical bone thickness and bone strength and inhibiting porosity.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2682396/

Osteoporosis in men: its pathophysiology and the role of ... Teriparatide is the only anabolic agent currently approved for treatment of osteoporosis in men. This paper summarizes the mechanism of action of teriparatide.

5. bonehealthandosteoporosis.org bonehealthandosteoporosis.org/patients/treatment/medicationadherence/teriparatide-parathyroid-hormone-pth-1-34-forteo/

Teriparatide Parathyroid Hormone (PTH) (1-34) (Bonsity® ... This medicine rebuilds bone and significantly increases bone mineral density. Teriparatide reduces the risk of spine and non-spine fractures.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03994172

Novel Combination Therapy for Osteoporosis in Men The study has two secondary objectives: (1) assess the effects of combination of TPTD (PTH 1-34) + placebo vs TPTD + oral calcimimetic cinacalcet on FN BMD by ...

7. reporter.nih.gov reporter.nih.gov/search/EsdiPcAsjUm9wRFRUnu4kg/project-details/11116827

RePORT RePORTER - National Institutes of Health (NIH) | TPTD has great appeal for treating osteoporosis in men because it substantially improves bone mass, rebuilds the microarchitecture, improves bone strength, and ...

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/72/NCT03994172/ICF_000.pdf

Novel Combination Therapy for Osteoporosis in Men ... This study will test the safety and effectiveness of the medication teriparatide compared to the combination of teriparatide with a medication ...

9. withpower.com withpower.com/trial/phase-4-osteoporosis-6-2019-317b1

Combination Therapy for Osteoporosis in Men Teriparatide, a part of the combination therapy, is generally well tolerated and has a good safety profile, but it may cause side effects like high calcium ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/021318Orig1s054.pdf

CENTER FOR DRUG EVALUATION AND RESEARCH The primary objective was to collect safety data for teriparatide following the withdrawal of teriparatide treatment. Trial Design. GHBJ was ...