Protocol H9V-MC-GFRF: A Randomized, Double-Masked, Placebo-Controlled, Multicenter, Phase 2 Study to Evaluate the Safety and Renal Efficacy of LY2382770 in Patients with Diabetic Kidney Disease due to Type 1 or Type 2 Diabetes. Protocol H9V-MC-GFRF
Study H9V-MC-GFRF (GFRF) is a randomized, double-masked, placebo-controlled, multicenter
Phase 2 study designed to compare the safety and renal efficacy of LY2382770 to placebo in
patients with diabetic kidney disease (DKD) due to type 1 or type 2 diabetes. Approximately
400 patients who meet all eligibility criteria will be randomized equally to one of 4 treatment
groups, which are 3 separate LY2382770 dose arms and 1 placebo arm (investigational drugs).
The study includes a Screening/Qualification Visit, an optional Run-In Period of up to 4 months,
a 12-month Treatment Period to assess LY2382770 safety and renal efficacy,
and a 2-month Follow-Up Period to assess residual renal effects.
The study is divided into 2 overlapping parts. In Part A, up to approximately 32 patients will be randomized at sites in the United States with an interim analysis of PK and safety data performed after approximately 18 patients have received at least 3 doses of LY2382770. Initiation of Part B will follow this analysis; up to approximately 370
additional patients will be randomized at US and non-US sites. The intention is to investigate in
Part B the same 3 LY2382770 dose levels and placebo used in Part A unless results from the
interim analysis indicate the need for an adjustment in any of the 3 LY2382770 dose levels.
Respective data on safety, PK, PD, and renal efficacy will be combined across the 2 study parts
for interim and final analyses.
Patients with presumed DKD and significant proteinuria based on a 24-hour urine collection, despite
appropriate ACEi or ARB treatment, will be randomized to enrich the population with patients likely to
demonstrate significant rise in SCr over the course of 1 year. Investigational drug will be administered
at the research site over the initial 11 months of the treatment period. During the 12-month treatment
period, serial study visits will occur for administering investigational drug, assessing tolerability as
reflected by adverse events (AEs), collecting safety laboratory data, and acquiring blood and urine
samples that will be used to assess renal efficacy and explore biomarkers that may further inform issues
related to safety or efficacy. A follow-up-period visit to assess residual effects on SCr and first morning
urine PCR occurs 2 months after the treatment period.
 Men and women >=25 years of age with a diagnosis of type 1 or type 2
 Women not of childbearing potential as a result of surgery (hysterectomy or
bilateral oophorectomy at least 3 months prior to Screening/Qualification
Visit, or tubal ligation for at least 12 months prior to Screening/Qualification
Visit) or menopause as follows.
* Women >=60 years of age are considered non-childbearing.
* Women 50 to 59 years, inclusive, must meet the surgical criteria or be
post-menopausal. Women with an intact uterus are deemed postmenopausal
if they have not taken oral contraception (low dose hormone
replacement therapy allowed) within the past 12 months and meet at least
one of the following conditions:
o spontaneous amenorrhea for at least the past 12 months
o spontaneous amenorrhea for at least 6 months but less than 12
months and a serum follicle-stimulating hormone (FSH) >40
* Women <50 years must meet the surgical criteria.
 Stable overt DKD, as defined by a diagnosis of diabetes and both of the following renal function criteria after appropriate equilibration on blood pressure therapy:
o Glomerular filtration function
Serum creatinine (SCr) 1.3 to 3.3 mg/dL (115 to 291 [MICRO-SYMBOL]mol/L) inclusive for women and 1.5 to 3.5 mg/dL (132 to 309 [MICRO-SYMBOL]mol/L) inclusive for men, or an eGFR 20 to 60 mL/min/1.73 m2 (fourvariable
simplified Modification of Diet in Renal Disease equation.
24-hour urine PCR >=800 mg/g (>=91 mg/mmol). Patients with urine PCR values ranging from 600 to 799 mg/g (68 to 90 mg/mmol) may provide a repeat sample.
 If treated with any diuretic drug, the dose(s) should be stable for
3 weeks prior to the Screening/Qualification Visit and 3 weeks prior to
the end of the Treatment Period and the Follow-up Period.
 Stable use of blood pressure medication and acceptable cuff blood
pressure as defined by the following criteria:
1. receiving the maximal labeled dose of an ACEi or ARB, or a submaximal dose (including not receiving therapy) that the Principal Investigator documents is appropriate for the patient[Single Quote]s
medical condition. The ACEi or ARB must be administered for >=3 months, the same dose used for >=2 months, and the dose not expected to change until the patient completes the trial.
2. stable doses of any other blood pressure medication (including diuretic therapy) for >=3 weeks.
3. seated cuff systolic blood pressure (SBP) <=150 mm Hg and diastolic blood pressure (DBP) <=90 mm Hg.
 Patients participating in the optional Run-In Period for any reason other than to complete cancer screening must meet both of the following renal function criteria prior to qualfiying for randomization
(that is, investigational drug randomization):
1. stable renal function as indicated by a repeat SCr measurement within 25% of the value obtained from the Screening Visit or 2 consecutive values obtained a minimum of 10 days and a
maximum of 21 days apart that are within 25% of each other.
2. 24-hour urine PCR >=1200 mg/g (>=136 mg/mmol). Patients with urine PCR values ranging from 1000 to 1199 mg/g (113 to 135 mg/mmol) may provide a repeat sample.
 Willingness to discontinue antihypertensive medications such as the renin inhibitor aliskiren, aldosterone antagonists, or ACEi and ARB dosed in combination.