To evaluate the effects of SB-751689 on the time to radiographic healing, defined as the interval in days between the occurrence of the radial fracture and the time of complete bridging and/or disappearance of fracture line at 3 of the following 4…
ID
Source
Brief title
Condition
- Bone disorders (excl congenital and fractures)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective
To evaluate the effects of SB-751689 on the time to radiographic healing,
defined as the interval in days between the occurrence of the radial fracture
and the time of complete bridging and/or disappearance of fracture line at 3 of
the following 4 cortices: dorsal, volar, radial, or ulnar.
Secondary outcome
Secondary objectives
1. To evaluate the safety and tolerability of SB-751689 administered for a
period of 12 weeks compared with placebo
2. To evaluate the dose regimen- and concentration-response relationships for
SB-751689 on:
* Serum PTH and calcium concentrations
* Biomarkers of bone turnover: serum cross-linked C-terminal telopeptide 1
chain of type I collagen (CTX), procollagen type 1 N-propeptide (P1NP),
bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC) concentrations
3. To evaluate radiographically:
* The baseline incidence of radio-ulnar joint involvement and radiocarpal joint
involvement
* The effects of SB-751689 on anatomical deformity of the wrist
4. To evaluate the effects of SB-751689 on the clinical assessment of healing
as defined by presence and/or absence of pain and swelling, and
range-of-motion.
5. To evaluate the effects of SB-751689 on mass grip strength, and to compare
the hand grip strength on both injured and un-injured hands as measured by the
JAMAR hand dynamometer
6. To evaluate the effect of SB-751689 on patient quality of life as assessed
by the Short Form 36 (SF-36)
7. To assess the effect of SB-751689 on patient activities as measured by the
Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire
Background summary
SB-751689 is a potent, selective calcium sensing receptor (CaR) antagonist.
Blocking calcium receptor activity on the parathyroid gland by SB-751689 will
stimulate a transient rise in endogenous parathyroid hormone (PTH) secretion.
Fractures are the largest problem facing individuals with bone disease. Wrist
fractures are the most commonly occurring fracture in women under the age of 75
in the United States (US) and Northern Europe. The worldwide incidence of
wrist fractures is not well known. The estimated lifetime risk of a wrist
fracture in women is 16% [Thorpe, 2006]. Currently, no systemic compound is
approved for the treatment of fracture healing. The proposed study design
focuses on closed fractures of the distal radius. While these fractures are
often viewed as simple, the treatment of them has evolved over time and
standard of care may vary regionally. The one agreed upon goal of therapy is
to restore functional anatomy with restoration of hand function. The
demonstrated effects of SB-751689 to release PTH and increase bone formation
have led to the proposed hypothesis in this study and may bridge the gap of an
unmet need for an effective oral anabolic agent to enhance fracture healing.
Study objective
To evaluate the effects of SB-751689 on the time to radiographic healing,
defined as the interval in days between the occurrence of the radial fracture
and the time of complete bridging and/or disappearance of fracture line at 3 of
the following 4 cortices: dorsal, volar, radial, or ulnar.
Study design
This is a Phase IIa randomized, double-blind, placebo-controlled,
parallel-group, multicenter, proof-of-concept study assessing the efficacy and
safety of SB-751689 in accelerating the healing of a closed fracture of the
distal radius. Study subjects will be adult men and women.
The study consists of 3 phases: a Screening period of 5 days or less in which
subject eligibility is determined (Screening Day -1 to -5), a Treatment Phase
of 12 weeks duration in which subjects will make visits to the clinic at Day 0
(Baseline) and Weeks 1, 2, 3, 4, 5, 6, 8, 12, and a Follow-up phase in which
subjects will make a single visit to the clinic 4 weeks after the last dose of
study medication (Week 16).
Intervention
The doses selected for the study are: SB-751689 at 400 mg once daily, 200 mg
twice daily, or placebo for 12 weeks.
Study burden and risks
see answers to questions E7 -E9
Huis ter heideweg 62
3705 LZ Zeist
Nederland
Huis ter heideweg 62
3705 LZ Zeist
Nederland
Listed location countries
Age
Inclusion criteria
1. Informed Consent: Subject is willing and able to provide written informed consent
2. Fracture type: Extra-articular distal radius fractures AO/ASIF types 23-A2 and 23-A3 are permissible.
3. Fracture treatment: Received conservative treatment of the distal radius fracture, including closed reduction and immobilization device
4. Men or Women: Ambulatory males or females aged *35 to < 80 years of age who have sustained a closed, unilateral, fracture of the distal radius no more than 5 days prior to randomization.
5. Protocol compliance
Exclusion criteria
1. Timing of fracture: Any treatment of a fractured distal radius that occurred more than 5 days after the fracture sustaining injury
2. Fracture: All B- and C-type fractures (intra-articular) according to AO Fracture classification that would likely require open reduction and internal fixation
3. Prior fractures: Prior fracture of the same wrist as an adult
6. Bone metabolism: History or concurrent diseases affecting bone metabolism (e.g., osteomalacia, hyperparathyroidism, hyperthyroidism, etc.)
7. Skeleton: History of skeletal immaturity or pathologic (tumor-related) fracture
8. Arthritis
9 Thyroid hormone replacement, Subjects will be excluded if TSH levels are <0.1 or >10.0 mIU/L. If TSH is >4.5 to <10.0 mIU/mL, measure T4 and exclude the subject only if the T4 is outside the normal range
12. Malignancy: Malignant disease diagnosed within the previous 5 years or active peptic ulcer disease
14. Liver disease
15. Drug or alcohol abuse: Drug or alcohol abuse (past or current) within the previous 12 months
18. Surgical and medical conditions
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov |
| EudraCT | EUCTR2007-001477-29-NL |
| CCMO | NL17945.029.07 |