E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Benign prostatic hyperplasia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004446 |
E.1.2 | Term | Benign prostatic hyperplasia |
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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 |
To compare the effect of LY500307 once daily for 24 weeks versus placebo treatment in improving the IPSS in men with LUTS and prostatic enlargement secondary to BPH. |
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E.2.2 | Secondary objectives of the trial |
- To compare the effect of 24 weeks of LY500307 versus placebo treatment on the TPV as measured by TRUS. - To evaluate the effect of 24 weeks of LY500307 versus placebo treatment on Qmax. - To evaluate the effect of 24 weeks of LY500307 versus placebo treatment on: BPH-related QoL assessed by IPSS-QoL Index; and IPSS storage, voiding, and nocturia subscores. - To evaluate the effect of 24 weeks of LY500307 versus placebo treatment on PSA. - To evaluate LY500307 PK and factors affecting LY500307 exposure in men with LUTS and prostatic enlargement secondary to BPH. - To evaluate the relationship between LY500307 exposure and clinical efficacy as well as safety measures. - To assess the safety of LY500307 once daily for 24 weeks in the treatment of men with LUTS and prostatic enlargement secondary to BPH |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Only male patients are eligible to be included in the study and only if they meet all of the following criteria: [1] Present at the time of screening with a history of BPH based on the diagnostic criteria. [2] Agree to use a reliable method of birth control during the study and for 3 months following the last dose of study drug. [3] Are at least 45 years of age at the time of screening. [4] Have an IPSS ≥13 at placebo lead-in. [5] Have a TPV by TRUS ≥30 mL at placebo lead-in. [6] Show signs of bladder outlet obstruction as defined by a peak urinary flow rate ≥4 and ≤15 mL/sec (from a prevoid total bladder volume [assessed by ultrasound] of ≥150 to ≤ 550 ml and a minimum voided volume of 125 ml) at placebo lead-in. [7] Have a PSA ≥1.4 and ≤10 ng/mL at the time of screening. If, at screening, the patient’s PSA is >4 ng/mL, prostate cancer must be excluded via a documented prostate biopsy within 12 months of screening and prior to the start of the patient’s placebo lead-in. [8] Demonstrate a PVR ≤300 mL by ultrasound at placebo lead-in. [9] Have not received the following treatments within the specified time period (9a through 9f): [9a] Finasteride or dutasteride for at least 6 months prior to placebo lead-in. [9b] Any alpha-adrenergic antagonists for at least 4 weeks prior to placebo lead-in. [9c] Any other non-experimental BPH therapy (including an herbal preparation) for at least 4 weeks prior to placebo lead-in. [9d] Any other experimental or off-label BPH therapy such as injectable therapies with a protracted effect for at least 6 months prior to placebo lead-in. [9e] Any overactive bladder treatment for at least 4 weeks prior to placebo lead-in. [9f] Any ED treatment which may include oral PDE type 5 inhibitors or devices for at least 4 weeks prior to placebo lead-in. [10] Have a morning fasting TT concentration ≥300 ng/dL at screening. If the TT criterion is not met at screening, the patient may undergo 1 retest within 1 month of initial screening if active new patient screening is ongoing [11] If hyperlipidemic, based on history, be on stable statin treatment as determined by the investigator for at least 2 months prior to placebo lead-in. |
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E.4 | Principal exclusion criteria |
[1] Have any history of BPH-related invasive procedures (for example, TURP, open prostatectomy, and minimally invasive procedures that include thermal-based therapies, transurethral microwave treatment, transurethral needle ablation, and stents). [2] Have active cardiovascular disease as evidenced by the following (2a through 2d): [2a] Recent MI, unstable angina, stroke or TIA within 6 months of placebo lead-in. [2b] Recent coronary intervention that includes coronary artery bypass surgery, percutaneous coronary artery intervention, or stent placement within 6 months of placebo lead-in. [2c] Recent history of positive stress tests without any written documentation of effective intervention within 6 months of placebo lead-in. [2d] Evidence of heart disease categorized as ≥Class III functional classification of NYHA within 6 months of placebo lead-in. [3] Have known or suspected history of prostate cancer, breast cancer, or other clinically significant neoplastic disease (other than squamous cell or basal cell carcinoma of skin). [4] Have a history of deep venous thrombosis or pulmonary embolism disease. [5] Have moderate to severe renal insufficiency. [6] Have a hemoglobin A1c (HbA1c) >9.0%. [7] Are on testosterone replacement therapy, or drugs that influence the hypothalamus-pituitary-gonadal axis, which may include any estrogen preparation, SERMs, GnRH agonists/antagonists, or androgen receptor antagonists within 1 month prior to screening. Patients on stable doses of thyroid replacement therapy will be allowed in this study. [8] Are on pharmacological treatment other than statins for hyperlipidemia. [9] Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. [10] Are Lilly employees. [11] Are currently enrolled in, or discontinued within the last 30 days (at screening) from, a clinical trial involving an investigational drug or device or off-label use of a drug or device (other than the study drug used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. [12] Have completed or withdrawn from this study or have completed or withdrawn from any other study investigating LY500307. [13] Are unable, unreliable, and/or unwilling to provide informed consent, make themselves available for the duration of the study, and refuse to comply with the procedures and study restrictions. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The mean change in IPSS total score from baseline to endpoint. |
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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 | 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 | Yes |
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.8.5.1 | Number of sites anticipated in the EEA | 20 |
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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Last visit of the last subject undergoing the trial. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |