A Study to Assess the Effect of AK3280 on Renal Function in Healthy Subjects

Study Overview
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Brief Summary
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AK3280 is being developed to further improve the long-term efficacy and tolerability of treatment options for patients with fibrotic disorders.This study will evaluate the effect of AK3280 treatment on renal function and safety, and the PK of AK3280 compared with placebo in healthy subjects.

Official Title
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A Phase I, Randomised, Double-blind, Placebo-controlled Study to Assess the Effect of Multiple Oral Doses of AK3280 on Renal Function in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: AK3280
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to give full written informed consent for participation in the study. Healthy male or female subject aged 18-45 years inclusive. Body Mass Index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2。 Clinically normal medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator in agreement with the Medical Monitor. With normal renal function defined as mean plasma eGFR ≥80 mL/min/1.73 m2 at screening. Male subjects and applicable female subjects must agree to use effective contraceptive methods to prevent drug exposure of a partner and pregnancy. Exclusion Criteria: History of allergy to iohexol or other contrast media, to iodine or to shellfish. History of any clinically significant disease or disorder or any other condition that in the opinion of the Investigator renders them unsuitable to participate in the study. Regular use of any prescribed or non-prescribed medication within two weeks prior to the (first) administration of IMP. Any significant elevation at screening or on Day -2 of liver or urinary or serum or plasma renal test results. Subjects with poor venous access. Subjects who have smoked cigarettes (including vapour cigarettes), cigars, and/or used nicotine-containing products within 3 months prior to their screening visit. Positive screen for a drug of abuse or alcohol at screening or prior to administration of the IMP. Subjects who have not abstained from caffeine-containing beverages or products from at least 48 hours prior to screening. An abnormal diet within the 30 days prior to the first study drug dose. Any use of protein powders, xanthine and/or taurine containing energy drinks within 48 hours prior to screening. Blood donation (or corresponding blood loss) during the three months prior to screening. Employees of the study unit or their family members, students who are working in the study unit, or family members of the Investigator or Sponsor. Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK3280 (Cohort 1)<br>Subjects in Cohort 1 are administered with an oral dose of 100 mg AK3280 b.i.d from Day 1 to Day 14. | Drug: AK3280<br>* Active Substance: AK3280, Pharmaceutical Form: Tablet, Route of Administration: Oral<br>|
| Experimental: AK3280 (Cohort 2)<br>Subjects in Cohort 2 are orally administered with AK3280 q.d. or b.i.d from Day 1 to Day 14. The dose adjustment for Cohort 2 will be based on the emerging data from previous cohort. | Drug: AK3280<br>* Active Substance: AK3280, Pharmaceutical Form: Tablet, Route of Administration: Oral<br>|
| Experimental: AK3280 (Cohort 3)<br>Subjects in Cohort 3 are orally administered with AK3280 q.d. or b.i.d from Day 1 to Day 14. The dose adjustment for Cohort 3 will be based on the emerging data from previous cohorts. | Drug: AK3280<br>* Active Substance: AK3280, Pharmaceutical Form: Tablet, Route of Administration: Oral<br>|
| Placebo Comparator: Placebo<br>For assessment of the Adverse Event (AE) profile, there are placebo controls in each dose cohort. | Drug: Placebo<br>* Active Substance: Placebo, Pharmaceutical Form: Tablet, Route of Administration: Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Directly measured absolute glomerular filtration rate (mGFR) results. | The effect of AK3280 treatment on GFR is measured by iohexol plasma clearance. | Days -1, 7, and 14. | 
| Change from baseline mGFR results. | To compare the difference of effect of AK3280 treatment on GFR. | Days 7 and 14. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency, intensity, and seriousness of Adverse Events (AEs) | An AE can be any unfavorable and unintended sign (including an abnormal safety laboratory finding), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. | From Day -1 to Day 28. | 
| Change in blood renal function biomarkers | Blood renal function biomarkers include cystatin C, beta-trace protein, p-myoglobin, etc. | Screening, Days -2, 7, 14, and 21. | 
| Change in urine renal function biomarkers | Urine renal function biomarkers include electrolytes, albumin, alpha1-microglobulin, etc. | From Day -1 to Day 21. | 
| Maximum Observed Plasma Concentration (Cmax) | The maximum observed plasma concentration of AK3280 and its major metabolite, AK3280-M2. | Days 1, 7, and 14. | 
| Concentration at the end of the dosing interval (Ctau) | The concentration of AK3280 and its major metabolite, AK3280-M2, at the end of the dosing interval. | Days 1, 7, and 14. | 
| trough plasma concentration (Ctrough) | The trough observed plasma concentration of AK3280 and its major metabolite, AK3280-M2. | Days 1, 7 and 14. | 
| trough plasma concentration (Ctrough) | The trough observed plasma concentration of AK3280 and its major metabolite, AK3280-M2. | Days 1, 7, and 14. | 
| Area under the plasma concentration-time curve from time zero up to time (AUC 0-t) | The area under the plasma concentration-time curve from time zero up to the last analytically quantifiable concentration of AK3280. | Days 1, 7, and 14. |