E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063024 |
E.1.2 | Term | Sarcopenia |
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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 main objective of this Phase IIA POC study is to evaluate the efficacy, safety, and tolerability of MK-0773 in elderly sarcopenic women. 1) To assess the effect of 6 months of treatment with MK-0773 on muscle strength, as determined by bilateral leg press, relative to placebo. 2) To assess the effect of 6 months of treatment with MK-0773 on total lean body mass (LBM), as determined by DEXA, relative to placebo. 3) To assess the safety and tolerability of 6 months of treatment with MK-0773
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E.2.2 | Secondary objectives of the trial |
1) To assess the effect of 6 months of treatment with MK-0773 on muscle power, as determined by stair climbing power, relative to placebo. 2) To evaluate the effect of 6 months of treatment with MK-0773 on mediolateral body sway with eyes open, relative to placebo. 3) To evaluate the effect of 6 months of treatment with MK-0773 on the short physical performance battery (SPPB) tests and its component, gait speed. 4) To evaluate the effect of 6 month of treatment with MK-0773 on self reported physical function (AM-PAC). 5) To perform endpoint validation analysis on performance-based and self-reported physical performance measures to identify optimal functional endpoints for Phase IIb and Phase III studies.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is a woman 65 years of age on day of signing the informed consent. 2. Patient has an aLBM/Ht2, measured by DEXA, > 1 SD below the mean of a healthy young adult population (peak). 3. Patient has self-reported difficulty in climbing 10 steps or walking ¼ mile outside on level ground without resting, or an AM-PAC physical movement score <66. 4. Patient has an SPPB score that is 1-9. 5. Patient is mentally competent - has scored ≥21 on the Folstein's Estate Examination (MMSE) at screening (Visit 1) and in the opinion of the Investigator is able to understand and follow study procedures. 6. Patient is judged to be in satisfactory health based on medical history, physical examination, ECG, and laboratory screening evaluations. 7. Patient has adequate organ function as indicated by the following laboratory values (Table 2-1) at screening (Visit 1): 8. Patient liver function tests are all within the normal range.
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E.4 | Principal exclusion criteria |
Patient has: •neuromuscular diseases (Parkinson's disease, amyotrophic lateral sclerosis, stroke affecting lower extremity function & muscular dystrophy), rheumatoid arthritis, conditions causing significant muscular/joint pain or significantly limits mobility (e.g. polymyalgia rheumatica, polymyositis, & fibromyalgia). Patient with conditions like osteoarthritis can participate unless pain limits performing study procedures. Patients with polymyalgia affecting only limited parts of upper body (i.e. neck, shoulder) can participate. •chronic lung disease limiting mobility due to respiratory function, or has another condition that impacts assessing improved muscle strength/ function, or has epilepsy, multiple sclerosis or focal lesions. •axis I psychiatric disorders in the 6 months prior to screening •inadequately treated depression or mental/legal incapacitation, or significant emotional problems at study start. •another neurological/psychiatric condition affecting ability to give informed consent and/or can impact cognitive function. •unstable angina or NYHA Class III or IV congestive heart failure or has uncontrolled hypertension (i.e., sitting systolic blood pressure >160 mmHg and/or sitting diastolic blood pressure >100 mm Hg). •clinically significant postural hypotension (i.e., drop of 20 mm Hg in systolic blood pressure or increase of 20 beats/minute after 5 mins standing). •a history of marked baseline prolongation of QT/QTc interval, or additional risk factors for Torsades de Pointes, or concomitant use of medications prolonging QT/QTc interval. •symptomatic peripheral arteriovascular disease likely to affect patients' mobility & ability to perform study procedures •significant cardiovascular disease, including any known history of myocardial infarction. •history of any cancer, except: adequately treated superficial basal or squamous cell carcinoma of skin or cervical carcinoma in situ; or solid tumor definitively treated without history of recurrence for at least 5 years prior to screening. •taken anabolic steroids, dehydroepiandrosterone, androstenedione, any drug altering testosterone metabolism within 12 months before screening or rGH in the 12 months prior to screening. Tamoxifen also prohibited due to its suppressive effects on androgen levels. •taken glucocorticoids at supraphysiological doses within 2 months before screening . Inhaled & topical glucocorticoids not excluded. •taken strong inhibitor/inducer of CYP3A4, within 2 weeks before screening or anticipates using these during study. •taken neuroleptic medications in the 6 months prior to screening. Hypnotics not excluded. Taking parathyroid hormone or vitamin D active metabolites. •Cushing's syndrome or disease not cured for at least 12 months, or has Addison's disease. •had bilateral adrenalectomy or any vestibular disorders. •requires walking aid to perform study procedures. Patients using walking aids are allowed in the study; however they must be able to perform most study procedures without an assistive device. It is permissible for the patient to use a walking device for the SPPB if she's not comfortable performing walk test without assistive device. •malabsorption syndrome or infections/ conditions predisposing to immunological suppression or immunodeficiency, including HIV infection. •hirsutism, and / or patient has severe facial acne or patient has androgenetic alopecia. •polycythemia, or untreated severe obstructive sleep apnoea, or uncontrolled diabetes, or HDL <40 mg/dL, or albumin <3.0 g/dL at the time of screening. •experienced unintentional weight change of >5% of the oldest recorded weight within the one year prior to screening or has a BMI >35. •primary hyperparathyroidism or active thyroid disease, demonstrated by abnormal serum TSH and free T4 at screening. •experienced acute illness within 30 days before screening affecting lower extremity function/patient's ability to participate in study. •performed vigorous exercise in 3 months before screening or plans to substantially change level of physical activity during study. •is unable to adhere to study procedures & dosing regimen possibly be due to untreated visual/hearing impairments; cannot swallow large pills; cannot keep appointments or plans to relocate during the study; inability to perform the one repetition maximum bilateral leg press procedure at Visit 1 •is at time of signing informed consent, a user of recreational/illicit drugs, or has recent history of drug/alcohol abuse/dependence. •a concurrent disease, or laboratory abnormality which would make patient inappropriate for entry into study. •is unable to adhere to the study procedures and dosing regimen which may be due to inability to comply with study drug regimen.
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E.5 End points |
E.5.1 | Primary end point(s) |
This is a 6-month study. The muscle strength determined by bilateral leg press will be measured at screening, randomization (Month 0), and Months 1, 3, and 6; the lean body mass (LBM) will be measured using DEXA at screening, Months 0, 3, and 6. The primary endpoints of interest will be the change from baseline in bilateral leg press and total lean body mass (LBM) at Month 6. |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | 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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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An interim efficacy analysis will be conducted when 50% of expected completers (approximately 40 per treatment group) complete the 6 month study. The study will be stopped if the treatment effects on both LBM and leg press are negative relative to placebo (point estimates of differences between MK-0773 and placebo are less than 0. The variability of the primary endpoints will also be checked and the sample size may be increased to ensure the study has sufficient power.
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial days | 1 |