Gemini is being evaluated in a placebo controlled, single dose, escalating dose study to evaluate the safety and tolerability of intravenous Gemini in adult subjects with stage 3 or 4 chronic kidney disease. Pharmacokinetics will be evaluated and measurements of the effect of Gemini on pharmacodynamic activity will be measured to assess changes in potential pharmacodynamic markers.
Design: Randomized, Placebo Controlled, Single Blind, Single-Ascending Dose Study in Patients with Stage 3-4 CKD. This study is planned as a placebo controlled, single dose, escalating dose study to evaluate the safety and tolerability of intravenous Gemini in adult subjects with stage 3 or 4 chronic kidney disease. This study will enroll up to 40 subjects in up to 5 cohorts. Each cohort will consist of 8 unique subjects, 6 assigned to Gemini and 2 assigned to placebo. All subjects will provide written informed consent and be screened for eligibility before enrollment. All eligibility criteria must be met prior to dosing. On Day 1, each study subject will receive a single IV dose (each total dose volume = 20 mL) via syringe pump for at least 10 minutes but not longer than 15 minutes and as per the institution's standard method. Time 0 starts once the entire dose is administered and the line has been flushed to ensure any residual drug is delivered. A Safety Review Committee (SRC) will assess safety and tolerability including AEs, after at least 6 subjects in each cohort have completed Day 8 to determine the subsequent cohort dose. If a grade 3 or higher adverse event is not experienced, as determined by the SRC, or the criteria for stopping dosing has not been met at a given cohort dose level, dose escalation will proceed to the next cohort and dose level. Dosing will continue until any cohort experiences a dose limiting toxicity (DLT), defined as a dose that causes any grade 3 or higher adverse event, or stopping criteria is met or the highest dose as determined in the Phase 1 study has been tolerated. If a dose is stopped due to a DLT or stopping criteria, cohorts scheduled at a higher dose will not be utilized. The SRC will meet to review safety and tolerability data and may determine if a lower dose can be given. This dose will be documented in the minutes and a dose recommendation memo which will be provided to the clinical sites. Once the maximum tolerated dose is determined, the dose will be repeated (Cohort 4) for a total of 16 subjects dosed at the highest level tolerated. The repeated dose cohort will consist of 8 unique subjects, 6 assigned to Gemini and 2 assigned to placebo. If the maximum tolerated dose is reached within the first 2 cohorts, the dose will be repeated until a minimum of 32 subjects are enrolled. If the highest dose determined in the Phase 1 study is tolerated, optional higher dosing of may be administered as determined by the SRC, or the same dose will be repeated. All visits will be conducted as an outpatient or via telephone.
Single ascending intravenous dose infused once over 10-15 minutes.
Intravenous sugar solution infused in a single dose over 10-15 minutes.
California Institute of Renal Research
Chula Vista, California, United States
California Institute of Renal Research
La Mesa, California, United States
Clinical Advance Center, PLLC
San Antonio, Texas, United States
Effect of Gemini versus placebo on the incidence of treatment-emergent adverse events.
Collection of side effects reported by subjects.
Time frame: From time of dose to Day 8
Effect of Gemini vs placebo on electrical activity of the heart.
Safety measure for change in the electrical activity of the heart over a period of time using electrodes placed on the skin and recorded by electrocardiogram (ECG) after resting for at least 10 minutes in a quiet setting without distractions in a semi-supine position.
Time frame: From time of dose to Day 8
Effect of Gemini versus placebo on blood pressure.
Safety measure for change in blood pressure after 5 minutes of rest in a supine, semi-supine or sitting position.
Time frame: From time of dose to Day 8
Number of participants with abnormal laboratory hematology test results.
Clinically significant changes in blood hematology levels.
Time frame: From time of dose to Day 8
Number of participants with abnormal laboratory chemistry tests results.
Clinically significant changes in blood chemistry levels.
Time frame: From time of dose to Day 8
Number of participants with abnormal laboratory urine tests results.
Clinically significant changes in urine.
Time frame: From time of dose to Day 8
Effect of Gemini versus placebo on inflammation in the body.
Measurement of erythrocyte sedimentation rate in the blood.
Time frame: From time of dose to Day 8
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
40
Effect of Gemini versus placebo on inflammation.
Measurement of N-terminal pro b-type natriuretic peptide in the blood.
Time frame: From time of dose to Day 8
Effect of Gemini versus placebo on the inflammatory state of CKD subjects.
Measurement of highly sensitive C-reactive Protein in the blood.
Time frame: From time of dose to Day 8
Effect of Gemini versus placebo on kidney damage.
Measurement of urine albumin creatinine ratio.
Time frame: From time of dose to Day 8
Effect of Gemini versus placebo on heart rate.
Safety measure for change in heart rate (bpm) after 5 minutes of rest in a supine, semi-supine or sitting position.
Time frame: From time of dose to Day 8
Effect of Gemini versus placebo on body temperature.
Safety measure for change in body temperature (Celsius) after 5 minutes of rest in a supine, semi-supine or sitting position.
Time frame: From time of dose to Day 8
Effect of Gemini versus placebo on respiration.
Safety measure for change in respiration rate after 5 minutes of rest in a supine, semi-supine or sitting position.
Time frame: From time of dose to Day 8
Number of participants with abnormal physical exam findings.
Clinically significance changes in general appearance.
Time frame: From time of dose to Day 8
Number of participants with abnormal mental physical exam findings.
Clinically significant changes in mental status.
Time frame: From time of dose to Day 8
Number of participants with abnormal physical exam findings above the shoulders.
Clinically significant changes with HEENT (head, eyes, ears, nose, throat).
Time frame: From time of dose to Day 8
Number of participants with abnormal physical exam findings of the skin.
Clinically significant changes in the dermatologic system.
Time frame: From time of dose to Day 8
Number of participants with abnormal physical exam findings of the heart.
Clinically significant changes in the cardiovascular system.
Time frame: From time of dose to Day 8
Number of participants with abnormal physical exam findings of the lungs.
Clinically significant changes in the respiratory system.
Time frame: From time of dose to Day 8
Number of participants with abnormal physical exam findings of the digestive system.
Clinically significant changes in the gastrointestinal system.
Time frame: From time of dose to Day 8
Number of participants with abnormal physical exam findings of the body's support structure.
Clinically significant changes in the musculoskeletal system.
Time frame: From time of dose to Day 8
Number of participants with abnormal physical exam findings of the nervous system.
Clinically significant changes in the neurological system.
Time frame: From time of dose to Day 8
Peak observed concentration of Gemini.
Measurement of maximum observed concentration (Cmax) in blood over intervals of time.
Time frame: From time of dose to Day 8
Time for Gemini to reach to maximum observed concentration.
Measurement of time to maximum observed concentration (Tmax) over intervals of time.
Time frame: From time of dose to Day 8
Total amount of Gemini that enters the systemic circulation after administration.
Measurement of area under the concentration-time curve (AUC0-t) over intervals of time.
Time frame: From time of dose to Day 8
Total Gemini exposure across time.
Measurement of area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞) over intervals of time.
Time frame: From time of dose to Day 8
The amount of time required for the plasma concentration of Gemini to decline by 50% .
Measurement if apparent terminal elimination half-life (t1/2) over intervals of time.
Time frame: From time of dose to Day 8
Volume of Gemini required to be uniformly distributed throughout the body.
Measurement of blood volume of distribution (Vd) over intervals of time.
Time frame: From time of dose to Day 8
Rate which Gemini is removed from the human system.
Measurement of elimination rate constant (Kel) over intervals of time.
Time frame: From time of dose to Day 8