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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: AK3280; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden
    • CTC Clinical Trial Consultants AB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK3280 (Cohort 1); 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; Active Substance: AK3280, Pharmaceutical Form: Tablet, Route of Administration: Oral
Experimental: AK3280 (Cohort 2); 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; Active Substance: AK3280, Pharmaceutical Form: Tablet, Route of Administration: Oral
Experimental: AK3280 (Cohort 3); 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; Active Substance: AK3280, Pharmaceutical Form: Tablet, Route of Administration: Oral
Placebo Comparator: Placebo; For assessment of the Adverse Event (AE) profile, there are placebo controls in each dose cohort.	Drug: Placebo; Active Substance: Placebo, Pharmaceutical Form: Tablet, Route of Administration: Oral

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Ark Biosciences Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2019
• Primary Completion (Actual): September 9, 2020
• Study Completion (Actual): September 21, 2020

Study Registration Dates

• First Submitted: June 12, 2019
• First Submitted That Met QC Criteria: June 16, 2019
• First Posted (Actual): June 19, 2019

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: AK3280-4001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No