Trial Outcomes & Findings for The Use of Steovess/Binosto After Denosumab Discontinuation to Prevent Increase in Bone Turnover (NCT NCT04403698)

NCT ID: NCT04403698

Last Updated: 2024-12-13

Results Overview

Difference in bone turnover marker C-terminal telopeptide of type I collagen (CTX-I) after 48 weeks. Comparisons made within and between both treatment arms

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: 48 weeks
• Results posted on: 2024-12-13

Participant Flow

Participant milestones

Measure	Treatment Alendronate 70 mg Weekly for 24 Weeks Subject receiving alendronate treatment for 24 weeks (n = 15) Alendronate Effervescent Oral Tablet: At the earliest three months but no later than four months after the last denosumab injection, subjects were randomized to effervescent alendronate administered for 24 weeks	Treatment Alendronate 70 mg Weekly for 48 Weeks Subject receiving alendronate treatment for 48 weeks (n = 15) Alendronate Effervescent Oral Tablet: At the earliest three months but no later than four months after the last denosumab injection, subjects will be randomized to effervescent alendronate administered for 48 weeks
Overall Study STARTED	15	15
Overall Study COMPLETED	13	13
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Measure	Treatment Alendronate 70 mg Weekly for 24 Weeks Subject receiving alendronate treatment for 24 weeks (n = 15) Alendronate Effervescent Oral Tablet: At the earliest three months but no later than four months after the last denosumab injection, subjects were randomized to effervescent alendronate administered for 24 weeks	Treatment Alendronate 70 mg Weekly for 48 Weeks Subject receiving alendronate treatment for 48 weeks (n = 15) Alendronate Effervescent Oral Tablet: At the earliest three months but no later than four months after the last denosumab injection, subjects will be randomized to effervescent alendronate administered for 48 weeks
Overall Study Adverse Event	1	1
Overall Study Lost to Follow-up	1	0
Overall Study Protocol Violation	0	1

Baseline Characteristics

The Use of Steovess/Binosto After Denosumab Discontinuation to Prevent Increase in Bone Turnover

Baseline characteristics by cohort

Measure	Treatment Alendronate 70 mg Weekly for 24 Weeks n=15 Participants Subject receiving alendronate treatment for 24 weeks (n = 15) Alendronate Effervescent Oral Tablet: At the earliest three months but no later than four months after the last denosumab injection, subjects were randomized to effervescent alendronate administered for 24 weeks	Treatment Alendronate 70 mg Weekly for 48 Weeks n=15 Participants Subject receiving alendronate treatment for 48 weeks (n = 15) Alendronate Effervescent Oral Tablet: At the earliest three months but no later than four months after the last denosumab injection, subjects will be randomized to effervescent alendronate administered for 48 weeks	Total n=30 Participants Total of all reporting groups
Age, Continuous	63.3 years STANDARD_DEVIATION 7.7 • n=5 Participants	64.7 years STANDARD_DEVIATION 8.9 • n=7 Participants	64.0 years STANDARD_DEVIATION 8.2 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
mean treatment duration with denosumab (days)	813 days STANDARD_DEVIATION 165 • n=5 Participants	751 days STANDARD_DEVIATION 174 • n=7 Participants	782 days STANDARD_DEVIATION 170 • n=5 Participants
mean time since last denosumab injection (days)	89 days STANDARD_DEVIATION 7 • n=5 Participants	94 days STANDARD_DEVIATION 8 • n=7 Participants	91 days STANDARD_DEVIATION 8 • n=5 Participants
N-terminal propeptide of type I procollagen (PINP)	10.15 microgram/L STANDARD_DEVIATION 5.5 • n=5 Participants	8.97 microgram/L STANDARD_DEVIATION 10.6 • n=7 Participants	9.56 microgram/L STANDARD_DEVIATION 8.3 • n=5 Participants
C-terminal telopeptide of type I collagen (CTX-I)	0.057 ng/ml STANDARD_DEVIATION 0.03 • n=5 Participants	0.071 ng/ml STANDARD_DEVIATION 0.06 • n=7 Participants	0.064 ng/ml STANDARD_DEVIATION 0.05 • n=5 Participants
Bone mineral density hip	0.85 g/cm2 STANDARD_DEVIATION 0.10 • n=5 Participants	0.80 g/cm2 STANDARD_DEVIATION 0.08 • n=7 Participants	0.83 g/cm2 STANDARD_DEVIATION 0.11 • n=5 Participants
Bone mineral density spine	1.16 g/cm2 STANDARD_DEVIATION 0.11 • n=5 Participants	1.11 g/cm2 STANDARD_DEVIATION 0.16 • n=7 Participants	1.14 g/cm2 STANDARD_DEVIATION 0.13 • n=5 Participants

PRIMARY outcome

Timeframe: 48 weeks

Difference in bone turnover marker C-terminal telopeptide of type I collagen (CTX-I) after 48 weeks. Comparisons made within and between both treatment arms

Outcome measures

Measure	24 Weeks n=15 Participants Subject receiving alendronate treatment for 24 weeks (n = 15)	48 Weeks n=15 Participants Subject receiving alendronate treatment for 48 weeks (n = 15)
CTX-I (C-terminal Telopeptide of Type I Collagen ) Bone Turnover Marker Levels Baseline	0.05 ng/ml Standard Error 0.06	0.06 ng/ml Standard Error 0.06
CTX-I (C-terminal Telopeptide of Type I Collagen ) Bone Turnover Marker Levels Week 48	0.63 ng/ml Standard Error 0.33	0.33 ng/ml Standard Error 0.33

PRIMARY outcome

Timeframe: 48 weeks

Difference in Bone Turnover Marker N-terminal propeptide of type I procollagen (PINP) After 48 Weeks. Comparisons are made both within and between both treatment arms.

Outcome measures

Measure	24 Weeks n=15 Participants Subject receiving alendronate treatment for 24 weeks (n = 15)	48 Weeks n=15 Participants Subject receiving alendronate treatment for 48 weeks (n = 15)
PINP (N-terminal Propeptide of Type I Procollagen) Bone Turnover Marker Levels Baseline	8.1 microgram/L Standard Error 0.41	4.6 microgram/L Standard Error 0.41
PINP (N-terminal Propeptide of Type I Procollagen) Bone Turnover Marker Levels Week 48	78.9 microgram/L Standard Error 0.44	39.5 microgram/L Standard Error 0.44

SECONDARY outcome

Timeframe: 48 weeks

The number of patients that do not maintain C-terminal telopeptide of type I collagen (CTx-I) levels within the bone turnover marker reference range at week 48.

Outcome measures

Measure	24 Weeks n=15 Participants Subject receiving alendronate treatment for 24 weeks (n = 15)	48 Weeks n=15 Participants Subject receiving alendronate treatment for 48 weeks (n = 15)
Number of Patients With CTX-I (C-terminal Telopeptide of Type I Collagen )Levels Above the Reference Range at Week 48	5 Participants	0 Participants

SECONDARY outcome

Timeframe: 48 weeks

The number of patients that do not maintain N-terminal propeptide of type I procollagen (PINP) levels within the bone turnover marker reference range at week 48

Outcome measures

Measure	24 Weeks n=15 Participants Subject receiving alendronate treatment for 24 weeks (n = 15)	48 Weeks n=15 Participants Subject receiving alendronate treatment for 48 weeks (n = 15)
The Number of Patients PINP (N-terminal Propeptide of Type I Procollagen) Above Reference Range at Week 48	5 Participants	0 Participants

SECONDARY outcome

Timeframe: 48 weeks

Difference in bone mass density at the spine after 48 Weeks. Comparisons are made both within and between both treatment arms

Outcome measures

Measure	24 Weeks n=15 Participants Subject receiving alendronate treatment for 24 weeks (n = 15)	48 Weeks n=15 Participants Subject receiving alendronate treatment for 48 weeks (n = 15)
Bone Mass Density at the Spine After 48 Weeks Baseline	1.16 g/cm2 Standard Error 0.03	1.11 g/cm2 Standard Error 0.03
Bone Mass Density at the Spine After 48 Weeks Week 48	1.10 g/cm2 Standard Error 0.03	1.11 g/cm2 Standard Error 0.03

SECONDARY outcome

Timeframe: 48 weeks

Difference in Bone Mass Density at the hip After 48 Weeks. Comparisons are made both within and between both treatment arms.

Outcome measures

Measure	24 Weeks n=15 Participants Subject receiving alendronate treatment for 24 weeks (n = 15)	48 Weeks n=15 Participants Subject receiving alendronate treatment for 48 weeks (n = 15)
Bone Mass Density at the Hip After 48 Weeks Baseline	0.85 g/cm2 Standard Error 0.03	0.80 g/cm2 Standard Error 0.03
Bone Mass Density at the Hip After 48 Weeks Week 48	0.85 g/cm2 Standard Error 0.03	0.81 g/cm2 Standard Error 0.03

Adverse Events

Alendronate 24 Weeks

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Alendronate 48 Weeks

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Alendronate 24 Weeks n=15 participants at risk Subject receiving alendronate treatment for 24 weeks and daily oral supplements of calcium and vitamin D for 48 weeks (n = 15)	Alendronate 48 Weeks n=15 participants at risk Subject receiving alendronate treatment for 48 weeks daily oral supplements of calcium and vitamin D (n = 15)
Gastrointestinal disorders Colonic ulcers	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.	0.00% 0/15 • Adverse events data was collected during the 48 weeks of the trial duration.

Other adverse events

Measure	Alendronate 24 Weeks n=15 participants at risk Subject receiving alendronate treatment for 24 weeks and daily oral supplements of calcium and vitamin D for 48 weeks (n = 15)	Alendronate 48 Weeks n=15 participants at risk Subject receiving alendronate treatment for 48 weeks daily oral supplements of calcium and vitamin D (n = 15)
Cardiac disorders Arterial hypertension	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.
Infections and infestations Infections	20.0% 3/15 • Number of events 3 • Adverse events data was collected during the 48 weeks of the trial duration.	26.7% 4/15 • Number of events 7 • Adverse events data was collected during the 48 weeks of the trial duration.
Gastrointestinal disorders stomach and stool problems	33.3% 5/15 • Number of events 9 • Adverse events data was collected during the 48 weeks of the trial duration.	40.0% 6/15 • Number of events 8 • Adverse events data was collected during the 48 weeks of the trial duration.
Musculoskeletal and connective tissue disorders muscular pain and joint pain	26.7% 4/15 • Number of events 6 • Adverse events data was collected during the 48 weeks of the trial duration.	33.3% 5/15 • Number of events 8 • Adverse events data was collected during the 48 weeks of the trial duration.
Nervous system disorders Headache and dizziness	20.0% 3/15 • Number of events 3 • Adverse events data was collected during the 48 weeks of the trial duration.	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.
Respiratory, thoracic and mediastinal disorders Cough (non-infectious)	0.00% 0/15 • Adverse events data was collected during the 48 weeks of the trial duration.	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.
Skin and subcutaneous tissue disorders Itch	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.	0.00% 0/15 • Adverse events data was collected during the 48 weeks of the trial duration.
Ear and labyrinth disorders Throat pain	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.	0.00% 0/15 • Adverse events data was collected during the 48 weeks of the trial duration.
Eye disorders Blurry vision and eye dryness	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.	13.3% 2/15 • Number of events 2 • Adverse events data was collected during the 48 weeks of the trial duration.
General disorders General malaise	0.00% 0/15 • Adverse events data was collected during the 48 weeks of the trial duration.	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.
Musculoskeletal and connective tissue disorders Bone fractures	0.00% 0/15 • Adverse events data was collected during the 48 weeks of the trial duration.	0.00% 0/15 • Adverse events data was collected during the 48 weeks of the trial duration.
Cardiac disorders Hypercholesterolemia	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.	0.00% 0/15 • Adverse events data was collected during the 48 weeks of the trial duration.
Cardiac disorders Atrial fibrillation	0.00% 0/15 • Adverse events data was collected during the 48 weeks of the trial duration.	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.
Skin and subcutaneous tissue disorders Hair loss	0.00% 0/15 • Adverse events data was collected during the 48 weeks of the trial duration.	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.
Ear and labyrinth disorders Tinnitus	0.00% 0/15 • Adverse events data was collected during the 48 weeks of the trial duration.	6.7% 1/15 • Number of events 1 • Adverse events data was collected during the 48 weeks of the trial duration.

Additional Information

Prof. dr. Ruth Wittoek

Study Principal Investigator Ghent Universitary Hospital

Phone: +329 332 25 20

Email: Ruth.Wittoek@Ugent.be

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place