A Study to Evaluate the Safety, Tolerability, PK and PD of AP303 in DKD Patients

NCT06666283 | Recruiting Phase 1 DMC

• 1 other identifier: AP303-PK-03
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The study will be a single center, double-blind, randomized, placebo-controlled study to evaluate the safety, tolerability, PK and PD of AP303 following 2-week oral administration to Diabetic Kidney Disease patients.

Conditions

Diabetic Kidney Disease

Outcome Measures

Primary Outcomes (31)

• Cmax

  Maximum observed plasma concentration

  Day 1, Day 14

• Tmax

  Time to maximum observed plasma concentration

  Day 1, Day 14

• AUC0-24h

  Area under the plasma concentration versus time curve up to 24 hours

  Day 1

• AUC0-last

  Area under the plasma concentration versus time curve up to the last measurable concentration

  Day 1

• AUC0-inf

  Area under the plasma concentration versus time curve extrapolated to infinity

  Day 1

• AUC0-t

  Area under the plasma concentration-time curve for a dosing interval

  Day 14

• t1/2

  Apparent terminal half-life, computed as ln(2)/λz

  Day 1, Day 14

• CL/F

  Apparent oral clearance calculated from Dose/ AUC0-inf

  Day 1

• V/F

  Apparent volume of distribution of oral drug

  Day 1, Day 14

• Cav

  Average plasma concentration

  Day 14

• Ctrough

  Trough plasma concentration

  Day 3-14

• Rac

  Ratio of accumulation

  Day 3-14

• Incidence and severity of adverse events

  Incidence and severity of adverse events

  Day 1-28

• Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results

  Incidence of laboratory abnormalities, based on hematology, clinical chemistry, coagulation and urinalysis test results

  Day 1-28

• Effect of AP303 on ECG parameters

  Change of Heart rate in beats/min

  Day 1-28

• Effect of AP303 on ECG parameters

  change of QT in ms

  Day 1-28

• Effect of AP303 on ECG parameters

  Change of PR in ms

  Day 1-28

• Effect of AP303 on ECG parameters

  Change of QRS in ms

  Day 1-28

• Effect of AP303 on ECG parameters

  Change of QTcF in ms

  Day 1-28

• Effect of AP303 on ECG parameters

  Change of QTcB in ms

  Day 1-28

• Vital signs（Systolic blood pressure）

  Change of systolic blood pressure

  Day 1-28

• Effect of AP303 on physical examination result

  Number of pariticipants with abnormal physical examination findings by nature and severity

  Day 1-28

• Body weight

  Change of body weight

  Day 1-28

• Vital signs (Diastolic blood pressure)

  Change of diastolic blood pressure

  Day1-28

• Vitlal signs (Body temperature)

  Change of body temperature

  Day 1-28

• Effect of AP303 on ECG parameters

  Number of participants with abnormal QTcB.

  Day 1-28

• Effect of AP303 on ECG parameters

  Number of participants with abnormal QTcF

  Day 1-28

• Effect of AP303 on ECG parameters

  Number of participants with abnormal QRS

  Day 1-28

• Effect of AP303 on ECG parameters

  Number of participants with abnormal PR

  Day 1-28

• Effect of AP303 on ECG parameters

  Number of participants with abnormal QT

  Day 1-28

• Effect of AP303 on ECG parameters

  Number of participants with abnormal heart rate

  Day 1-28

Secondary Outcomes (4)

• Fasting glucose

  Baseline, Days 6, 10, 14 and 28

• Fasting lipid profile

  Baseline, Days 6, 10, 14 and 28

• Serum creatinine

  Baseline, Days 6, 10, 14 and 28

• eGFR

  Baseline, Days 6, 10, 14 and 28

Study Arms (2)

AP303

EXPERIMENTAL

Drug: AP303 150μg

Placebo

PLACEBO COMPARATOR

Drug: Placebo 150μg

Interventions

AP303 150μg DRUG

AP303 Tablet 150μg QD

AP303

Placebo 150μg DRUG

Placebo Tablet 150μg QD

Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants, ≥30 years of age at the time of signing the informed consent form.
• BMI (body mass index) 18-30 kg/m².
• Patient has a clinical diagnosis of Type 2 Diabetes Mellitus and is taking at least one type of hypoglycemic drugs, before screening visits, the doses of hypoglycemic drugs, including insulin, need to be stable for at least two weeks..
• Patient must be on a stable dose of angiotensin converting anzyme inhibitior (ACEI) or Angiotensin II receptor blockers (ARB) for at least 4 weeks prior to screening.
• Hemoglobin A1c ≥6.5% but ≤10.5% at the screening visit.
• Estimated GFR ≥30 mL/min/1.73m² but \< 60 mL/min/1.73m² at the screening visit.
• Urinary albumin to creatinine ratio ≥ 30 mg/g at the screening visit.

You may not qualify if:

• Chronic kidney disease other than type 2 diabetic kidney disease.
• Patient receiving corticosteroid immunotherapy or other immunosuppressants (such as calcineurin inhibitors ciclosporin, cyclophosphamide, or mycophenolate mofetil) in the past 3 months before screening.
• Recently having acute kidney injury or received renal surgery within the last 6 months before screening visit, or have received renal transplantation.
• Congestive heart failure classified New York Heart Association (NYHA) class II to IV within the last 3 months before the screening visit.
• Peripheral edema above the ankle level at the screening or randomization visit.
• Confirmed (based on the average of 2 separate resting blood pressure measurements in a sitting position, after at least 5 minutes rest) systolic BP greater than 160 or less than 90 mmHg, and diastolic BP greater than 100 or less than 50 mmHg at screening.
• Myocardial infarction, acute coronary syndrome, stroke or transient ischemic attack, cardiovascular surgery within 6 months prior to the screening visit.
• Abnormalities of ECG parameters and abnormal shape of ECG wave on screening ECG: e.g.
• QTc interval (QTcF \> 450 ms for male and QTcF \> 470 ms for female) based on the average interval on triplicate ECGs obtained after 5 minute's rest in a supine position
• Notable resting bradycardia (mean HR \< 40 bpm)
• Notable resting tachycardia (mean HR \> 100 bpm)
• ECG with QRS and/or T wave judged to be unfavorable for a consistently accurate QT measurement (e.g., neuromuscular artifact that cannot be readily eliminated, indistinct QRS onset, low amplitude T wave, merged T- and U-waves, prominent U waves)
• Any other significant abnormality
• Implantation of cardiac pacemaker or clinically significant arrhythmia, e.g. atrial fibrillation, atrial flutter, right or left bundle branch block, Wolf-Parkinson-White Syndrome.
• Current or previous treatment with a thiazolidinedione (e.g., medications containing pioglitazone or rosiglitazone, like Actos, Avandia, ActoplusMet, Avandamet, Avandaryl), PPARa agonist (like fenofibrate) or any dual/multiple PPARa/g agonist (e.g., Chiglitazar Sodium) in the 3 months preceding screening visit.

Sponsors & Collaborators

• Alebund Pharmaceuticals: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100009, China

RECRUITING

MeSH Terms

Conditions

Diabetic Nephropathies

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Hong Zhang

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

• Ying Gao

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuran Zhang

CONTACT

+8613661548603; yuran.zhang@alebund.com

Jue Huang

CONTACT

+8613764056397; jue.huang@alebund.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2024
• First Posted: October 30, 2024
• Study Start: February 27, 2025
• Primary Completion: September 25, 2025
• Study Completion: September 25, 2025
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)