MULTICENTRE, RANDOMIZED, OPEN-LABEL, TWO-ARM PARALLEL GROUPS, ACTIVE CONTROLLED STUDY DESIGN TO DEMONSTRATE EFFICACY AND TOLERABILITY OF CLODRONATE 200 MG/4 ML SOLUTION FOR INTRAMUSCULAR USE WITH 1% LIDOCAINE EVERY OTHER WEEK VS CLODRONATE 100 MG/3,3ML SOLUTION FOR INTRAMUSCULAR USE WITH 1% LIDOCAINE ONCE-WEEK IN A 1-YEAR TREATMENT PERIOD OF WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS

• Register: EUCTR
• Last refreshed on: 17 June 2013
• Main ID: EUCTR2010-022060-13-PL
• Date of registration: 27/06/2011
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: MULTICENTRE, RANDOMIZED, OPEN-LABEL, TWO-ARM PARALLEL GROUPS, ACTIVE CONTROLLED STUDY DESIGN TO DEMONSTRATE EFFICACY AND TOLERABILITY OF CLODRONATE 200 MG/4 ML SOLUTION FOR INTRAMUSCULAR USE WITH 1% LIDOCAINE EVERY OTHER WEEK VS CLODRONATE 100 MG/3,3ML SOLUTION FOR INTRAMUSCULAR USE WITH 1% LIDOCAINE ONCE-WEEK IN A 1-YEAR TREATMENT PERIOD OF WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS
• Scientific title: MULTICENTRE, RANDOMIZED, OPEN-LABEL, TWO-ARM PARALLEL GROUPS, ACTIVE CONTROLLED STUDY DESIGN TO DEMONSTRATE EFFICACY AND TOLERABILITY OF CLODRONATE 200 MG/4 ML SOLUTION FOR INTRAMUSCULAR USE WITH 1% LIDOCAINE EVERY OTHER WEEK VS CLODRONATE 100 MG/3,3ML SOLUTION FOR INTRAMUSCULAR USE WITH 1% LIDOCAINE ONCE-WEEK IN A 1-YEAR TREATMENT PERIOD OF WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS
• Date of first enrolment: 18/11/2011
• Target sample size: 326
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022060-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Bulgaria, Italy, Poland

Contacts

• Name: Clinical Study Manager
• Affiliation: Chiesi Farmaceutici S.p.A.

• Name: Clinical Study Manager
• Affiliation: Chiesi Farmaceutici S.p.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1.Subject’s written informed consent obtained prior to any study-related procedures;
2.Postmenopausal (any menses in the last 5 years) female subjects >= 50 years old with lumbar T-score < -2,5 and > -4 or femoral-neck T-score < -2,5 and > -3;
3.At least three intact vertebrae between L1 and L4 and two evaluable vertebrae for DXA;
4.Patients treated according to the non-pharmacological standard of care;
5.Patients with the possibility and willingness to take the i.m. injections

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 196
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 130

Exclusion criteria:
BMI < 19 kg/m2;
2. History of: ever use of intravenous bisphosphonates or strontium ranelate, more than 12 months of bisphosphonates (oral and intramuscular) continuatively , or any use of bisphosphonates (oral and intramuscular) within the last year, rhPTH use (recombinant human PTH) in the last 2 years, calcitonin use within the past 3 months, raloxifene and tamoxifen in the last 6 months or for more than 12 months in the last 2 years, fluoride (> 1 mg/die) for at least a month within the past 5 years;
3. Use of estrogen (oral or patch) for more than 1 month in the last 6 months or more than 12 months in the last 2 years;
4. Serious diseases of the oral cavity and surgery and/or dental implant from less than a month or planned in the next 12 months;
5. Type 1 or uncontrolled type 2 diabetes mellitus (defined as hemoglobin A1C >10,0), or currently using insulin;
6. Family history of malignant hyperthermia;
7. Heart disease, particularly bradyarrhythmias and heart failure; Adams-Stokes syndrome, Wolff-Parkinson-White syndrome or severe degrees of sinoatrial, atrioventricular or intraventricular block, acute cardiac decompensation;
8. History of kidney failure or renal insufficiency (creatinine > 2,0 mg/dl)
9. History of stroke in the last 6 months or uncontrolled hypertension;
10. History of hypercalciuria;
11. History of hypercalcemia, sarcoidosis, hyperparathyroidism, hyperthyroidism or hypothyroidism (except for patients in conditions of euthyroidism taking stable dose of thyroid hormone from at least 6 weeks);
12. History of any malignancy except for epithelioma considered cured;
13. Patients currently treated with systemic corticosteroids or > 2000 mcg beclomethasone dipropionate or equivalent daily;
14. Patients currently treated with antiepileptic drugs and/or anticoagulants or treated in the last 6 months or for more than 12 months in the last 2 years;
15. Patients current treated with propanolol, cimetidine or digitalis drugs;
16. History of alcohol or drug abuse;
17. Allergy, sensitivity or intolerance to study drugs (included lidocaine or other amide-type local anaesthetics) or excipients;
18. Subjects unlikely to comply with the study protocol or unable to understand the nature and scope of the study but also the possible benefits or unwanted effects of the study treatments.
19. Subjects who received any investigational new drug, or participated in clinical study within the last 12 weeks.
20. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
21. Femoral-neck T-score <-3


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Postmenopausal osteoporosis
MedDRA version: 14.1 Level: PT Classification code 10031285 Term: Osteoporosis postmenopausal System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

Intervention(s)

Product Name: Anhydrous disodium clodronate with lidocaine
Product Code: N/A
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Clodronic acid
CAS Number: 22560-50-5
Other descriptive name: Clodronate disodium
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: Lidocaine
CAS Number: 91484-71-8
Other descriptive name: 2-diethylamino-N-(2,6-dimethylphenyl)-ethanamide
Concentration unit: ml millilitre(s)
Concentration type: equal
Concentration number: 4 ml-

Trade Name: CLODY
Product Name: Anhydrous disodium clodronate with lidocaine
Product Code: N/A
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Clodronic acid
CAS Number: 22560-50-5
Other descriptive name: CLODRONATE DISODIUM
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: 2-(diethylamino)-N-(2,6-dimethylpheny...
CAS Number: 91484-71-8
Other descriptive name: LIDOCAINE
Concentration unit: ml millilitre(s)
Concentration type: equal
Concentration number: 3,3 ml-

Primary Outcome(s)

Main Objective: To demonstrate that disodium clodronate 200 mg/4 ml solution for i.m. use with 1% lidocaine administered every other week is not-inferior to disodium clodronate 100 mg/3,3 ml for i.m. use with 1% lidocaine administered once-week in terms of lumbar Bone Mineral Density (BMD).

Secondary Objective: The secondary objectives of the study will be:
To assess the efficacy of the two investigational study drugs on femoral-neck BMD, serum level of turnover bone biomarkers (CTX and BALP) and treatment compliance.
To assess the safety of the two investigational study drugs as regards local pain and tolerability assessment, frequency of adverse events, laboratory parameters and vital signs (heart rate and blood pressure).

Primary end point(s): The primary efficacy variable is the value of lumbar BMD after 1-year treatment. DXA scan will be evaluated by a centralised laboratory

Timepoint(s) of evaluation of this end point: V0 and V5

Secondary Outcome(s)

Secondary end point(s): ?Lumbar BMD after 24-week treatment (carried out in a centralised laboratory);
?Femoral-neck BMD after 24-week and 1-year treatment (carried out in a centralised laboratory);
?Biochemical markers of bone turnover after 24 and 48 weeks of treatment (carried out in a centralised laboratory);
?Compliance evaluated at each visit after randomization visit.

Timepoint(s) of evaluation of this end point: V0, V3, V4 and V5

Secondary ID(s)

MC/PR/9900/004/10

Source(s) of Monetary Support

Chiesi Farmaceutici S.p.A.