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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: AK3280; Drug: Placebo

• Registration Number: NCT03990688
• Lead Sponsor: Shanghai Ark Biopharmaceutical Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-12
• Study First Submitted QC: 2019-06-16
• Study First Posted: 2019-06-19
• Study Start: 2019-10-03
• Primary Completion: 2020-09-09
• Study Completion: 2020-09-21
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-08
• Last Update Posted: 2021-06-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AK3280 (Cohort 2)	AK3280	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.
Placebo	Placebo	For assessment of the Adverse Event (AE) profile, there are placebo controls in each dose cohort.
AK3280 (Cohort 3)	AK3280	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.
AK3280 (Cohort 1)	AK3280	Subjects in Cohort 1 are administered with an oral dose of 100 mg AK3280 b.i.d from Day 1 to Day 14.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Frequency, intensity, and seriousness of Adverse Events (AEs)	From Day -1 to Day 28.	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.
Change in blood renal function biomarkers	Screening, Days -2, 7, 14, and 21.	Blood renal function biomarkers include cystatin C, beta-trace protein, p-myoglobin, etc.
Change in urine renal function biomarkers	From Day -1 to Day 21.	Urine renal function biomarkers include electrolytes, albumin, alpha1-microglobulin, etc.
Maximum Observed Plasma Concentration (Cmax)	Days 1, 7, and 14.	The maximum observed plasma concentration of AK3280 and its major metabolite, AK3280-M2.
trough plasma concentration (Ctrough)	Days 1, 7, and 14.	The trough observed plasma concentration of AK3280 and its major metabolite, AK3280-M2.
Area under the plasma concentration-time curve from time zero up to time (AUC 0-t)	Days 1, 7, and 14.	The area under the plasma concentration-time curve from time zero up to the last analytically quantifiable concentration of AK3280.
Concentration at the end of the dosing interval (Ctau)	Days 1, 7, and 14.	The concentration of AK3280 and its major metabolite, AK3280-M2, at the end of the dosing interval.

Trial Locations

Locations (1)

CTC Clinical Trial Consultants AB; 🇸🇪 Uppsala, Sweden