Trial · Interventional

CompletedPhase 4Results postedRegistry data

Novel Combination Therapy for Osteoporosis in Men

Short name Osteo-Men

NCTNCT03994172Other idENDB-012-17FOther id1 IO1 CX001514-01A2

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 4
Enrollment: 40 participants (actual)
Sponsor: VA Office of Research and Development · Fed
Design: Randomized · Triple masking
Countries: 1 country
United States
Start: 1 Jul 2019
Primary completion: 30 Jun 2025
Completion: 30 Jun 2025
First posted: 21 Jun 2019
Last update posted: 3 Sept 2026
Conditions: Male Osteoporosis

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2020202220242026

Ph 4
Osteo-Men
NCT03994172
1 Jul 2019 to 30 Jun 2025

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

Osteoporotic fractures are a key health problem in older men. Although there are drugs approved to treat osteoporosis in men \[bisphosphonates, denosumab, and teriparatide (TPTD) or PTH(1-34)\], there is a lack of knowledge on how to use them effectively. TPTD is a potent bone anabolic drug, meaning that it builds bone mass. However, doctors do not know if it should only be used as single drug or whether it can be more effectively combined to achieve the most benefit? 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 improve bone strength by stimulating PTH receptors (PTH-Rs) on the membranes of bone-forming cells or osteoblasts (OBs). Calcimimetics are drugs that activate calcium receptors (CaSRs) in OBs. CaSRs in OBs participate in new bone formation. Daily injections of TPTD, given along with a calcimimetic drug (called NPS-R568), over 6 weeks markedly improved bone mineral density (BMD) and structure in mice. This study will test whether the combined activation of PTH-Rs and CaSRs (by the combination treatment of TPTD+calcimimetic cinacalcet) in men will produce greater bone forming responses than PTH-R activation alone (TPTD+placebo). The study has two aims and will be done in 48 men with low bone mass: (1) to determine the effects of 11 months treatment with TPTD+cinacalcet vs TPTD+placebo on BMD and bone metabolism by assessing lumbar spine BMD (primary endpoint), femoral neck BMD, and levels of the bone formation marker serum N-terminal pro-peptide of type 1 collagen; (2) to determine the biochemical responses by blood tests in men who receive the combination of TPTD+cinacalcet compared to men who get TPTD+placebo treatment. This is done by quantifying acute and chronic changes in serum calcium and PTH levels right after these drugs are given and how much calcium is excreted in the urine over time, with both treatment regimens. This study will help to understand whether an effective combination therapy in mice will prove to be effective in men.

Interventions

Teriparatide or human parathyroid hormone (PTH) 1-34Drug
CinacalcetDrug
placebo tabletDrug
Calcium citrate tabletDietary supplement
Vitamin D3Dietary supplement

Arms2

Experimental
Combination Therapy Arm: Teriparatide (TPTD) + the Calcimimetic Cinacalcet
Combination therapy 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.
Placebo comparator
Monotherapy Arm: Teriparatide (TPTD) + Placebo
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.

Primary outcomes1

Outcomes the sponsor listed as primary.

Effects of Treatment With TPTD+Cinacalcet Compared to TPTD+PBO on Lumbar Spine BMD in Men With Low Bone Mass
Time frame · 48 weeks
Registry description
Hypothesis 1a proposes that BMD responses to combined TPTD+cinacalcet are greater than those induced by TPTD+PBO. LS BMD typically responds quickly and robustly to TPTD and is the 1o endpoint of the trial. DXA measurements will be performed and analyzed by standard protocols at baseline and at the end of the trial. Subjects will be treated for 11 months (48 weeks). All subjects will receive Ca and vitamin D3 supplements throughout the trial. The percentage change in LS BMD from baseline to 48 week/11 months of treatment will be the variable/endpoint that is calculated.

Secondary outcomes(2)

Effects of Treatment With TPTD+Cinacalcet Compared to TPTD+PBO on Serum P1NP in Men With Low Bone Mass
Time frame · 12 weeks
Registry description
Hypothesis 1b proposes that serum P1NP (N-terminal pro-peptide of type 1 collagen), a highly sensitive marker of bone turnover and specifically of bone formation, will increase to a greater extent in men treated with TPTD+cinacalcet vs TPTD+PBO. Serum P1NP is the best validated biomarker of TPTD action and responds rapidly and robustly to anabolic therapy. This secondary endpoint will be assessed at the 3 month/12 week visit in the fasting state on morning lab tests (prior to study drug administration). The endpoint is a blood test of bone formation marker comparing results from Day 1/Randomization Visit to Study Visit at 3 months/12 weeks. The percentage change in this bone formation marker will be the variable that will constitute this secondary endpoint.
Effects of Treatment With TPTD+Cinacalcet Compared to TPTD+PBO on Femoral Neck BMD in Men With Low Bone Mass
Time frame · 48 weeks
Registry description
Hypothesis 1a also proposes femoral neck BMD responses to combined TPTD+cinacalcet are greater than those induced by TPTD+PBO. FN BMD responses tend to be smaller than LS BMD responses to TPTD and this aim will test whether the combination therapy (CaSR activation + PTH-R activation) will produce larger BMD responses at the FN site in men with low BMD. The percentage change in FN BMD from baseline to 48 week/11 months of treatment will be the variable/endpoint that is calculated.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· 48 weeks

Effects of Treatment With TPTD+Cinacalcet Compared to TPTD+PBO on Lumbar Spine BMD in Men With Low Bone Mass

Group	Value (percent change)	Spread
Combination Therapy Arm: Teriparatide (TPTD) + the Calcimimetic Cinacalcet	6.1	4.6
Monotherapy Arm: Teriparatide (TPTD) + Placebo	5.8	3.5

Secondary and other outcome results(5)

Secondary outcomeMean· 12 weeks

Effects of Treatment With TPTD+Cinacalcet Compared to TPTD+PBO on Serum P1NP in Men With Low Bone Mass

Group	Value (percent change)	Spread
Combination Therapy Arm: Teriparatide (TPTD) + the Calcimimetic Cinacalcet	175	98
Monotherapy Arm: Teriparatide (TPTD) + Placebo	171	129

Secondary outcomeMean· 48 weeks

Effects of Treatment With TPTD+Cinacalcet Compared to TPTD+PBO on Femoral Neck BMD in Men With Low Bone Mass

Group	Value (percent change)	Spread
Combination Therapy Arm: Teriparatide (TPTD) + the Calcimimetic Cinacalcet	0.4	5.7
Monotherapy Arm: Teriparatide (TPTD) + Placebo	2.4	4.0

Other pre specified outcomeMean· 8 hours during the Randomization Visit

Mean Serum Calcium During Acute Pharmacodynamic Testing

Group	Value (mg per deciliter)	Spread
Combination Therapy Arm: Teriparatide (TPTD) + the Calcimimetic Cinacalcet	9.25	0.37
Monotherapy Arm: Teriparatide (TPTD) + Placebo	9.26	0.31

Other pre specified outcomeMean· 48 weeks

Mean Serum Calcium During 48 Weeks of Study Visits

Group	Value (mg per deciliter)
Combination Therapy Arm: Teriparatide (TPTD) + the Calcimimetic Cinacalcet	9.25
Monotherapy Arm: Teriparatide (TPTD) + Placebo	9.35

Other pre specified outcomeMean· 48 weeks

Total Urinary Calcium Excretion During 48 Weeks of Study

Group	Value (mg per 24 hours)
Combination Therapy Arm: Teriparatide (TPTD) + the Calcimimetic Cinacalcet	211.6
Monotherapy Arm: Teriparatide (TPTD) + Placebo	156.6

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Combination Therapy Arm: Teriparatide (TPTD) + the Calcimimetic CinacalcetCombination therapy 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.	1 / 20	3 / 20	20 / 20
Monotherapy Arm: Teriparatide (TPTD) + PlaceboMonotherapy 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.	0 / 20	2 / 20	17 / 20

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: Male
Age: from 60 Years up to 85 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

Inclusion Criteria: * DXA BMD T-score \< or = -2.0 at either lumbar spine (LS), femoral neck (FN) or total hip (TH) sites; or DXA BMD T-score \< or = -1.5 with at least one additional important clinical risk factor for osteoporotic fracture \[e.g., fragility fracture after age 50 years; parental history of hip fracture; history of hypogonadism, prior glucocorticoid therapy (\>3 months prior), current smoking, prevalent vertebral fracture(s), or prior hyperthyroidism on stable treatment\] * At least 2 LS vertebral levels with reliable BMD values (i.e., at least 2 without compression or hardware) Exclusion Criteria: * Metabolic bone disease other than osteoporosis (e.g., Paget's disease, hyperparathyroidism) * Any osteoporosis drug therapy within 12 months; any prior course of TPTD for \> or = 3 months; any history of IV bisphosphonate therapy; oral bisphosphonate therapy exceeding 3 months in past 2 years; oral bisphosphonate treatment exceeding 2 years ever; or use of denosumab (within the past 3 years or \> 3 or = injections ever). * Oral glucocorticoid use (\> or = 5 mg prednisone) taken within 3 months prior to enrollment * Hypercalcemia (albumin-corrected serum \[Ca\] \>10.2 mg/dL), hypocalcemia (albumin-corrected serum \[Ca\] \<8.8 mg/dL), elevated intact PTH level, or hypercalciuria (urinary Ca \>300 mg/24 hours) at screening * 25 OH vitamin D levels \<20 ng/ml or \>80 ng/ml at screening * Estimated glomerular filtration rate \< 30 ml/min (chronic kidney disease (CKD) stage 4 or 5) * Cancer within past 5 years except for non-melanomatous skin cancers * History of skeletal radiation, prior history of osteosarcoma or bone metastases * Substance abuse (\>3 drinks/day), liver disease or impaired liver function (abnormal liver function tests defined as greater than 3 times the upper limit of normal), known cirrhosis, malabsorption * Poorly controlled diabetes (A1c \>9.0%) or current thiazolidinedione therapy * Drugs metabolized through CYP2D6 (e.g., flecainide, tricyclic antidepressants) and strong inducers or inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole) * Testosterone therapy with dose change within last 12 months; or androgen deprivation therapy within 12 months * Thyrotropin (TSH) level \< 0.01 * Congenital long QT syndrome, history of QT interval prolongation, family history of long QT syndrome or sudden cardiac death, and other conditions that predispose to QT interval prolongation and ventricular arrhythmia * Hypersensitivity to teriparatide or any excipients in Forteo * Use of other Ca-lowering drugs (e.g., calcitonin, bisphosphonates, denosumab) * Moderate to severe hepatic impairment * High risk for active urolithiasis, defined as having passed a kidney stone clinically within the last 5 years * Upper gastrointestinal (GI) bleeding with a history of a clinical episode of upper GI bleeding within last 10 years that was note definitively treated by a surgical procedure * Orthostatic hypotension or a known history of orthostatic hypotension documented in the chart or provided by the patient upon clinical history-taking * Impaired cardiac function either diagnosed symptomatic heart failure requiring medical therapy

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