A Phase II, Randomized, Cross-Over, Vehicle-Controlled, Double-Blind, Multicenter Study of the Safety, Pharmacodynamics, and Preliminary Efficacy of GHRP-1/AG in Subjects With ESRD on Hemodialysis

Study Overview
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Brief Summary
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Malnutrition and altered protein catabolism are serious problems in renal failure and hemodialysis (HD) patients. The purpose of this study is to characterize the safety of GHRP-1/AG in subjects with ESRD on HD; to characterize the pharmacodynamics (PD) of GHRP-1/AG in subjects with ESRD on HD by following GH and IGF-1; to describe the relationship between GHRP-1 PD and plasma concentrations of GHRP-1 and des-Ala-GHRP-1; and to evaluate the preliminary efficacy of GHRP-1/AG on nutritional status of subjects with ESRD on HD using subjective global assessment of malnutrition inflammation scores (MIS) and changes in caloric intake.

Detailed Description
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This is a randomized, cross-over, double-blind, vehicle-controlled study. Subjects will receive single subcutaneous injections of the active GHRP-1/AG study treatment and vehicle control (ATRIGEL delivery system) in a randomized sequence. Each injection will be followed by a 4-week period of treatment exposure and a 2-week period of washout/follow-up. Treatments will be administered on the 2nd dialysis day of a 3x/week dialysis schedule. The total duration of study participation will be 12 weeks. Safety will be followed throughtout the study with vital signs, electrocardiogram, clinical chemistry and hematology parameters, endocrine parameters, adverse events, and concomitant medications. PD effects of GHRP-1/AG will be evaluated by measuring GH, ICF-1, IGF-BP3, prolactin, and cortisol. Efficacy will be evaluated throughout the study with MIS, caloric intake, nPCR, dry weight, BMI, and albumin, BUN, creatinine, calcium, potassium, HGB, HCT, and CBC.

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: GHRP-1/AG 70 mg depot in ESRD
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with ESRD who have been on HD for at least 3 months and have a urea reduction rate (URR) of at least 65%. Subjects who are 18 to 70 years of age. Subjects who have a body mass index (BMI) less than 30, albumin greater than 3.3 g/dL, and MIS of 5 to 10 (inclusive). Exclusion Criteria: Subjects who have diabetes and are currently taking insulin. Subjects who have a history of or current significant central nervous system (CNS) disorders. Subjects who have active infection at baseline. Subjects who have active or unstable cardiac or arterial disease. Subjects who have uncontrolled tertiary hyperparathyroid condition. Subjects who have anemia. Subjects who have a history of hepatitis or current liver disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: GHRP-1/AG 70 mg depot in ESRD|nan|
|Other: Placebo|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital signs |  |  | 
| ECG |  |  | 
| clinical chemistry and hematology |  |  | 
| MIS |  |  | 
| caloric intake (protein, fat, carbohydrates, total) |  |  | 
| nPCR |  |  | 
| BMI and dry weight |  |  | 
| clinical laboratory parameters |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IGF-1, IGF-BP3, GH, prolactin, and cortisol plasma concentrations |  |  | 
| GHRP-1 and des-Ala-GHRP-1 plasma concentrations |  |  | 
| adverse events |  |  | 
| concomitant medications |  |  | 
| endocrine parameters |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End stage renal disease, Hemodialysis, Malnutrition, End stage renal disease (ESRD)