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Efficacy and Safety of Oral Salmon Calcitonin in Patients With Knee Osteoarthritis

Phase 3
Completed
Conditions
Osteoarthritis
Interventions
Drug: SMC021 Placebo
Registration Number
NCT00486434
Lead Sponsor
Nordic Bioscience A/S
Brief Summary

The purpose of this Phase III study is to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of patients with osteoarthritis of the knee.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1176
Inclusion Criteria
  • Medical history and symptoms of knee osteoarthritis
Exclusion Criteria
  • Any other disease or medication affecting the bone or cartilage.
  • Any clinical signs or laboratory evidence diseases, which in the Investigator's opinion would preclude the participant from adhering to the Protocol or completing the trial.

Other protocol defined inclusion/exclusion criteria may apply

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
2SMC021 PlaceboSMC021 Placebo, orally twice daily during 24 months
1SMC021 Oral CalcitoninSMC021 Oral Calcitonin, 0.8 mg twice daily during 24 months
Primary Outcome Measures
NameTimeMethod
Joint Space Width (JSW) in the Medial Tibiofemoral Knee Joint in Signal Knee Measured by X-ray After 24 Months.Change from baseline to 24 months

The signal knee was chosen prior to randomization based on which knee met the inclusion and exclusion criteria. The JSW is the space measured in mm between the 2 bones in the knee joint and this is assessed by x-ray. The JSW decreases with disease progression. The lower limit for participation in the trial were 2 mm JSW. There were no upper limit as long as inclusion and exclusion criteria were met. The outcome was measured as a change in JSW from baseline to month 24.

Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscore in the Signal KneeChange from baseline to 24 months

WOMAC is a self-administered set of standardized questionnaires to evaluate the condition of patients with osteoarthritis of the knee. The subject marks on a scale (1-100) the pain associated with performing each daily activity listed in the questionnaire. 0 is no pain (best), 100 is extreme pain (Worst). The total function sub score for the questions are then calculated. Total possible minimum sub score is 0, maximum is 500. The final outcome is the absolute change from baseline to 24 months. If the outcome is less that 0 there is improvement (less pain).

Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function Subscore in the Signal Knee.Change from baseline to 24 months

WOMAC is a self-administered set of standardized questionnaires to evaluate the condition of patients with osteoarthritis of the knee. The subject marks on a scale (1-100) the degree of difficulty for performing each daily function listed in the questionnaire. 0 is no difficulty (best), 100 is extreme difficulty (worst). The total function sub score for the questions are then calculated. Total possible minimum sub score is 0, maximum is 1700. The final outcome is the absolute change from baseline to 24 months. If the outcome is less that 0 there is improvement (less difficulty).

Secondary Outcome Measures
NameTimeMethod
Changes in Biochemical Markers of Bone & Cartilage Metabolism.From Baseline to Month 24

The central laboratory analyzed serum CTX-I (S-Crosslaps, Elecsys) and osteocalcin as well as urine CTX-I/creatinine and CTX-II/creatinine. It was originally planned that serum CTX-II would be measured, but this was not done.

Effect on Hand Osteoarthritis (OA) Assessed by X-ray & Questionnaire From Baseline to 24 MonthsBaseline and Month 24

To assess disease progression of OA affected joints, X-rays of both hands were performed \& assessed by two central readers (at Synarc). Hand OA was assessed by calculating total score for osteophytes, cyst erosion, \& joint space narrowing, each of which were based on sum of left and right hand X-ray analysis with possible scores of 0-66. The overall total score (possible range 0-198) was also used. Higher scores (closer to 66 or to 198 when using overall total score) imply a worse outcome. Hand analyses were based on double readings, and the mean was used in the analyses.

The AUStralian/CANadian Osteoarthritis Hand Index (AUSCAN) questionnaire was also used for assessment of hand OA. It measures pain (5 questions), stiffness (1 question) and difficulties with daily activities (9 questions) through a visual analogue scale (0-100mm; 0 = lowest score; 100 = highest score). Lower AUSCAN scores represent a better outcome. Change (from baseline to month 24) in these scores was calculated.

Nature and # of AEs Monitored Continuously During StudyFrom Baseline to Month 24

Adverse events were by system organ class of all patients.

Disease Progression in the Knee Evaluated by MRI.From Baseline to Month 24

Disease progression in the signal knee (cartilage volume and thickness) were evaluated by magnetic resonance imaging (MRI). MRIs were performed for patients from the sites in Ballerup, Denmark, the Czech Republic, and Romania using a quality controlled low-field 0.18T C-Span scanner from Esaote dedicated to the imaging of extremities. The same solenoid coil was used for all patients at a given site.

Trial Locations

Locations (9)

Centrum Osteoporozy i Chorób Kostno Stawowych, ul. Waryńskiego 6/2

🇵🇱

Bialystok, Poland

CCBR Poland

🇵🇱

Warsaw, Poland

CCBR Czech

🇨🇿

Pardubice, Czechia

CCBR Ballerup

🇩🇰

Ballerup, Denmark

CCBR Estonia

🇪🇪

Tallinn, Estonia

CCBR Romania

🇷🇴

Bucharest, Romania

CCBR Aalborg

🇩🇰

Aalborg, Denmark

CCBR Vejle

🇩🇰

Vejle, Denmark

CCBR Hong Kong

🇭🇰

Hong Kong, Hong Kong

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