| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Osteopenia
Please note this is not a study to investigate the use of the IMP for the treatment of osteopenia but rather to validate a non-invasive imaging technique for measuring early changes in bone in response to therapy. |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10049088 |
| E.1.2 | Term | Osteopenia |
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| 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 aim of this study is to investigate if 18F-fluoride PET can be used to assess the direct effects of treatment on bone turnover at the hip.
The primary objective is to compare changes in bone turnover at the hip measured by 18F-fluoride PET in postmenopausal women treated with teriparatide and untreated controls. |
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| E.2.2 | Secondary objectives of the trial |
To compare changes in bone turnover at the hip with changes at the lumbar spine in response to teriparatide treatment.
To compare changes in bone turnover at the spine and hip with changes in biochemical markers of bone turnover and changes in bone mineral density.
To examine test-retest variability of 18F-fluoride PET measurements at the hip. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects will be eligible for entry into the study if they meet all the following inclusion criterion:
• Ambulatory postmenopausal* women.
• Aged 50 to 85 years inclusive.
• Free of severe or chronically disabling condition.
• Without language barrier, cooperative, expected to return for all follow-up visits and who give written informed consent before entering the study.
• Lumbar spine, femoral neck and/or total hip BMD between 1 and 2.5 standard deviations below the average bone mineral density for young healthy women (i.e. T-score ≤-1 to > -2.5) as determined from the manufacturer’s database.
• Normal or clinically insignificant abnormal laboratory values.
• Normocalcemia Serum Calcium ≥2.15 mmol/l and ≤2.55 mmol/l.
• Vitamin D 25-(OH) Serum level of ≥15 ng/ml (37.4 nmol/L)
• Otherwise in good health as determined by past medical history, physical examination, vital signs, standard laboratory tests and urinalysis at screening and the opinion of the investigator.
• Screening BMI must be >18.5 and ≤30 and subjects must weigh at least 50 kg.
• At Screening vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed after the subject has rested for at least three (3) minutes, and again if clinically indicated after three (3) minutes in standing position. Vital signs should be within the following ranges:
o Tympanic (ear) temperature between 35.5 – 37.5 °C
o Systolic blood pressure, 90 – 160 mm Hg
o Diastolic blood pressure, 50 – 90 mm HG
o Pulse rate, 55 – 90 bpm
When blood pressure and pulse will be taken again after 3 minutes standing, there shall be no more than a 20 mm Hg drop in systolic or 10 mm Hg drop in diastolic blood pressure and increase in heart rate (>20 bpm) associated with clinical manifestation of postural hypotension.
All blood pressure measurements at other time-points should be assessed with the subject seated, unless stated otherwise in the protocol design, and utilizing the same arm for each determination.
• Ability to lie still in a PET scanner for 70 minutes
Definitions:
* Postmenopausal status is defined as:
• no vaginal bleeding for at least 12-months prior to enrolment in women with an intact uterus or
• a hysterectomy and/or bilateral oophorectomy 12-months after a naturally occurring menopause or
• a hysterectomy and/or bilateral oophorectomy prior to menopause and at least 12-months prior to enrolment with postmenopausal status defined biochemically by oestradial <73 pmol/L and FSH > 30 IU/L (confirmed prior to dosing).
• In women >50 and <60 years of age, FSH level > 30 IU/l (confirmed prior to dosing)
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| E.4 | Principal exclusion criteria |
Subjects will be excluded from the study if they meet any of the following criteria:
• Current or recent (within 1 year of enrolment) metabolic bone disorders such as Paget’s disease of bone, Cushing’s Syndrome, acromegaly, osteogenesis imperfecta, renal osteodystrophy, osteomalacia, any secondary causes of osteoporosis and/or bone loss, or serious illness affecting normal bone homeostasis.
• Current or recent (within 1 year of enrolment) disease which affects bone metabolism, such as hypoparathyroidism, hyperparathyroidism, or hyperthyroidism.
• Subjects with a history of hypothyroidism not on stable replacement therapy with levothyroxine (defined as no change of dose for at least 6-months prior to enrolment)
• Subjects with skeletal malignancies or bone metastases
• Recent (within 6-months of enrolment) fracture at any skeletal site.
• Significant osteoarthritis of the lumbar spine and/or hip(s) precluding a satisfactory DXA or 18F-fluoride PET scan.
• History of carcinoma in the previous 5 years or currently suspected carcinoma, with the exception of excised superficial lesions such as basal cell carcinoma and squamous cell carcinoma of the skin.
• Current or recent (within 1 year of enrolment) inflammatory bowel disease or malabsorption syndrome.
• Pre-existing hypercalcaemia
• Unexplained elevations of alkaline phosphatase.
• Current or recent (within 2 years of enrolment) nephrolithiasis or urolithiasis.
• Clinically significant renal, pancreatic, hepatic or cardiovascular disease, diabetes requiring pharmacotherapy indicated by:
o Clinically significant abnormal liver function tests such as SGOT, SGPT, GGT, alkaline phosphatase, or serum bilirubin
o Clinically significantly abnormal creatinine or BUN values or abnormal urinary constituents (e.g. albuminuria)
o Evidence of urinary obstruction or difficulty in voiding at screening
• History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory tests conducted at screening.
• Current or recent treatment (within 1 year of enrolment) with androgens or other anabolic steroids.
• Current or recent (within 1 year of enrolment) treatment with oestrogens (with or without progestins) or selective oestrogen receptor modulators (SERMs)
• Current or recent (within 1 year of enrolment) treatment with systemic corticosteroids, or orally inhaled or nasally inhaled corticosteroids in doses > 400 µg/day beclomethasone/day or equivalent.
• Current or previous treatment with IV or oral bisphosphonates, strontium ranelate, fluorides, calcitonin, teriparatide or PTH 1-84, aluminium supplements.
• Patients with 25-(OH) Vitamin D levels less than 15 ng/mL (37.4 nmol/L) prior to randomization
• Treatment with vitamin D or calcium supplements started less than one month prior to screening visit.
• Current or recent (within 1 year of enrolment) treatment with anticonvulsants.
• Subjects with a positive Hepatitis B surface antigen (HBsAg) or hepatitis C test result or a history of immunodeficiency diseases, including a positive HIV test result.
• Hypersensitivity to teriparatide or to any of the excipients.
• Prior external beam or implant radiation therapy to the skeleton.
• Poor medical or psychiatric risk for treatment in the opinion of the investigator.
• Subjects with anorexia nervosa, suspected bulimia (by history or physical) or obvious malnutrition
• Subjects exhibiting or with a history of any of the following signs or symptoms:
o High caffeine intake (more than 8 cups of coffee per day, or equivalent)
o Vertebral tenderness
o Surgical scar on neck suggestive of prior thyroid surgery
o Rachitic rosary or any bony deformities suggestive or prior rickets
o Café au lait spots (suggestive of McCune-Albright syndrome)
o Neuromuscular irritability (hypocalcemia)
• Smokers who report cigarette use of more than 20 cigarettes per day.
• Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations.
• Donation or loss of 400 ml or more of blood within 8 weeks prior to screening, or longer if required by local regulation.
Plasma donation within 7 days prior to first dosing. Hemoglobin levels below 12.0 g/dl at screening.
• Significant illness within two weeks prior to dosing.
• History of acute or chronic bronchospastic disease (including chronic obstructive pulmonary disease, treated or not treated)
• History of clinically significant drug allergy or history of atopic allergy (urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or drugs similar to the study drug.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary objective is to demonstrate a significant increase in the rate of bone formation, measured by 18F-fluoride PET, in the hip following 12-weeks of treatment with the anabolic agent teriparatide as compared to controls. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
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| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| 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 | No |
| 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
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| The end of the study is defined as the date that the last subject enrolled has their last study visit. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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