A 24-week, international, multi centre, randomised, double-blind, double-dummy, parallel group, phase IV clinical trial investigating changes in back pain in postmenopausal women with an osteoporosis related vertebral fracture(s) treated with either 100 µg PTH(1-84) daily or 70 mg alendronate weekly - RELIEF

Phase 1

• Conditions: Primary Postmenopausal Osteoporosis; MedDRA version: 9.1 Level: LLT Classification code 10031285 Term: Osteoporosis postmenopausal

• Registration Number: EUCTR2006-006064-32-GB
• Lead Sponsor: ycomed Danmark Aps

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-02-08
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 300

Inclusion Criteria

1. Has the subject given informed consent according to local requirements before any trial related activities? (A trial related activity is any procedure that would not have been performed during the routine management of the subject).
2. Is the subject at least 50 years of age?
3. Has the subject been postmenopausal for more than 3 years – in the judgement of the investigator?
4. Does the subject have a T-score = -1.5 SD; T-scores must be assessed by DXA at
either the lumbar spine L1-L4, with a minimum of two assessable vertebrae, or at the
total hip or at the femoral neck (existing DXA scans up to 3 months old at the time of
screening visit are accepted)
5. Does the subject have an X-ray verified vertebral fracture (reduction > 25% in anterior, middle or posterior height compared to adjacent vertebra) defined by Genant semi quantitative visual grading? (existing X-rays up to 6 weeks old at the time of screening visit are accepted)
6. Does the subject have chronic back pain which is considered to be related to at least one vertebral fracture with a height reduction of > 25% (chronic pain is defined as 3 months with back pain likely to be caused by the vertebral fracture(s))?
7. At the screening visit: does the subject assess the intensity of her back pain this morning before any use of analgesic medication to be 4 or more on the 11 point NRS.
8. At the randomisation visit: is the average of the last 7 days back pain assessments 4 or more on the 11 point NRS (captured in the i-diary system)?
9. Is the subject willing to call the i-diary system (using a free number) every day for the whole trial period and register the intensity of her back pain and number of falls?
10. Is the subject on a stable pain management regime in the judgement of the
investigator?
11. Is the subject currently taking calcium and vitamin D3 or is she willing to start such supplemental treatment and continue throughout the trial period, unless she develops hypercalcaemia or any other drug related side effect?
12. Has the subject been taking the minimum required supplemental daily dose of calcium (1,000 mg) and vitamin D3 (800 IU) for at least 14 days (after the screening visit) before blood sampling for eligibility evaluation?
13. Is the subject able to self-inject PTH(1-84), or have the injections with assistance from a helper?
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Has the subject within the last 3 months prior to the planned randomisation visit been treated with systemic anti-resorptive treatment (e.g. bisphosphonates, calcitonin, HRT (hormone replacement therapy) or SERM (selective estrogen receptor modulator))? Local estrogens vaginal suppository is allowed prior to and during trial participation.
If No (no treatment received) please proceed to exclusion criteria 2.
If Yes (treatment received), please proceed to criteria 1A and 1B below. The subject must fulfil (Yes to) either 1A or 1B, in order to be enrolled.

Onset of the anti-resorptive treatment has been:
1A within the last 6 months prior to the screening visit:
Is the subject willing to stop this treatment immediately?
(The screening period can serve as wash out period and must be at least 1 month).
or
1B more than 6 months prior to the screening visit:
Is the subject willing to stop this treatment immediately; and start a wash out period of at least 3 months prior to randomisation?
(The screening period (max 6 weeks) can serve as part of the 3 months).
2. Has the subject within the last 3 months prior to the planned randomisation visit been treated with strontium ranelate?
If No (no treatment received) please proceed to exclusion criteria 3.
If Yes (treatment received), please proceed to criteria 2A and 2B below. The subject must
fulfil (Yes to) either 2A or 2B, in order to be enrolled.
Onset of this treatment has been:
2A within the last 6 months prior to the screening visit:
Is the subject willing to stop this treatment immediately?
(The screening period can serve as wash out period and must be at least 1 month).
or
2B more than 6 months prior to the screening visit:
Is the subject willing to stop this treatment immediately; and start a wash out period of at least 3 months prior to randomisation?
(The screening period (max 6 weeks) can serve as part of the 3 months).
3. Has previous treatment with bisphosphonates been discontinued due to adverse events (side effects) related to this treatment?
Has the subject within the last 3 months prior to the planned randomisation visit been treated with:
4. fluorides?
5. teriparatide or PTH(1-84)? (previous treatment must not have exceeded 12 months in total)
6. glucocorticosteroids? Local, topical and inhalation steroids are permitted.
or has the subject been treated:
7. with any intravenous (iv.) bisphosphonates within the last 12 months
8. for cancer (other than basocellular skin cancer) within the last 5 years?
9. with radiation therapy to the skeleton ever?
or does the subject suffer from:
10. spondylolisthesis, intervertebral disc herniation, spinal stenosis or another spinal
disease, that –in the judgement of the investigator, can be the cause of the back pain?
11. active upper gastro-intestinal problems such as dysphagia, gastritis, duodenitis, ulcers or has a recent history (within the last year) of major gastrointestin

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to show that PTH(1-84) is superior to alendronate in reducing back pain intensity, over a 24-week treatment period in postmenopausal women with an osteoporosis related vertebral fracture(s). ;Secondary Objective: Secondary objective is to investigate any differences in patient reported outcomes between the two treatment arms over a 24-week treatment period in postmenopausal women with an osteoporosis related vertebral facture(s).;Primary end point(s): •Change in back pain intensity during 24 weeks of treatment, using a numerical rating scale (NRS)