E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
postmenopausal women with osteopenia (BMD T-score -2.5 < T ≤ -1.0) at one or more of the regions: the lumbar spine, femoral neck or total hip. |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to determine the efficacy of 3 different (200 µg, 1600 µg, 3200 µg) daily doses of a subcutaneous injection of GLP-2 on biochemical markers of bone turnover as compared to placebo treatment and whether there will be a favourable effect on net bone mineral density (BMD) between the GLP-2 and placebo treated women. Another objective is to evaluate the safety and tolerability of the tested doses during the 120-day treatment period as compared with placebo treatment. Furthermore, the clinical optimal dose(s) will be selected for the next phase of the clinical development |
|
E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
· Postmenopausal women age 55-75 who have been postmenopausal for at least 5 years since their last menstrual cycle. · Signed informed consent before any study specific procedure is performed. · BMD T-score between -2.5 < T ≤ -1.0 at one or more of the regions: lumbar spine, femoral neck or total hip. · Bone turnover assessed by measuring s-CTX. Reference range for this parameter is: s-CTX (0.439-1.351 ng/ml for Serum CrossLaps One Step ELISA and 0.504-1.224 ng/ml for Serum CTX Elecsys). · Non-obese with a BMI between 20.0-30.0 kg/m2. · Good physical and mental condition. · In the Investigator’s opinion, the subject is able to comply with the protocol and complete the study.
|
|
E.4 | Principal exclusion criteria |
· BMD T-score > -1.0 at all the regions: lumbar spine, femoral neck and total hip. · BMD T-score ≤ -2.5 at any of the regions: lumbar spine, femoral neck and total hip. Chronic administration of any prescription medication known to influence bone metabolism or the gastrointestinal system within the last 6 months: · Estrogens (also combined estrogen-progestin therapy). · SERMs (e.g. raloxifene, basedoxifene, tamoxifene, etc.). · Tibolone. · Calcitonin. · Vitamin D supplements in excess of 2000 IU daily. · PTH 1-34, 1-84, or other PTH fragments/analogs. · Anabolic steroids (natural and synthetic androgens, e.g. testosterone, nandrolone, mesterolon etc.). · Systemic glucocorticoids (local glucocorticoids are acceptable). · Remicade (infliximab) · Interferon and antiviral medication · Antiepileptics (e.g. valproate, phenytoin, primidon, tiagabin, etc.). · Azathioprin · Sandostatin · Bisphosphonates (oral and intravenous): – if used more than 3 years, then subject cannot be included. – if used less than 3 years and last dose less than 1 year ago, then subject cannot be included. – if used less than 3 months and last dose more than 1 year ago, then subject may be included. · Strontium or fluoride (oral or intravenous) within the last 3 years · History or evidence of any diseases known to influence bone or calcium metabolism. Potential alterations in bone turnover and calcium-regulating hormones will be assessed objectively by measuring PTH and vitamin D, respectively. Reference ranges for these parameters are: PTH (15.00 - 65.00 pg/ml) and vitamin D (47.7 - 144.0 nmol/l). · Gastrointestinal diseases and major operations in the gastrointestinal tract. · Secondary osteoporosis (osteoporosis due to other underlying conditions, such as metastasis, hyperthyroidism, hyperparathyroidism, chronic treatment with glucocorticoids). · Paget’s disease of bone. · Hypothyroidism. · Hypoparathyroidism. · Hypocalcaemia (albumin adjusted serum calcium below 2.13 mmol/L, (8.5 mg/dl)) · Rheumatoid arthritis. · Dermatomyositis. · Other metabolic bone disease (rickets and osteomalacia). · Genetic and dysplastic disorders (e.g. osteogenesis imperfecta, fibrous dysplasia, chondrodystrophy). · Any renal diseases causing impaired renal function as determined by s-creatinine > 0.12 mmol/l. · Any hepatic disease causing increases in serum concentrations of ASAT or ALAT more than x 2 the normal upper range values. · Diabetes mellitus. · Malignancy within the last 10 years, except for skin cancer (basal cell carcinoma). · Alcohol or drug abuse. · Any clinically significant findings, which the Investigator considers a potential source of complications for the subject.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoints of the study are the change in s-CTX following injection of GLP-2 versus placebo.
Additionally, the study intends to clarify whether the 120 day treatment with GLP-2 will give rise to any change in BMD at the spine over the 120 days, both within groups and between groups.
The primary safety endpoint of the study is that no serious adverse events can be related to the administration of GLP-2.
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 4 |