Study to Evaluate the Pharmacokinetic Characteristics of Pegylated Exenatide Injection (PB-119) in Subjects With Different Degrees of Renal Insufficiency and Matched Subjects With Normal Renal Function

NCT05328843 | Unknown Phase 1

• 1 other identifier: PB119109
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-dose, parallel grouping, open-label phase I clinical study to evaluate the PK characteristics and safety of single subcutaneous injection of PB-119 in subjects with different degrees of renal insufficiency and matched subjects with normal renal function.

Conditions

Type2Diabetes

Outcome Measures

Primary Outcomes (3)

• Primary PK parameters: AUC0-inf

  Plasma will be collected at predose(-30 min \~ 0 min) and 2 h (Day1), 4 h (Day1), 9 h (Day1), 15 h (Day1), 24 h (Day2), 30 h (Day2), 36 h (Day2), 40 h (Day2), 48 h(Day3) ), 60 h(Day3), 72 h(Day40), 96 h(Day5), 120 h(Day6), 144 h(Day7), 192 h (Day9) , 240 h (Day11), 288 h (Day13), 336 h (Day15)last detectable plasma concentration

  Up to 336 h(Day15) post-dose

• Primary PK parameters: AUC0-t

  Plasma will be collected at predose(-30 min \~ 0 min) and 2 h (Day1), 4 h (Day1), 9 h (Day1), 15 h (Day1), 24 h (Day2), 30 h (Day2), 36 h (Day2), 40 h (Day2), 48 h(Day3) ), 60 h(Day3), 72 h(Day40), 96 h(Day5), 120 h(Day6), 144 h(Day7), 192 h (Day9) , 240 h (Day11), 288 h (Day13), 336 h (Day15)last detectable plasma concentration

  Up to 336 h(Day15) post-dose

• Primary PK parameters: Cmax

  Plasma will be collected at predose(-30 min \~ 0 min) and 2 h (Day1), 4 h (Day1), 9 h (Day1), 15 h (Day1), 24 h (Day2), 30 h (Day2), 36 h (Day2), 40 h (Day2), 48 h(Day3) ), 60 h(Day3), 72 h(Day40), 96 h(Day5), 120 h(Day6), 144 h(Day7), 192 h (Day9) , 240 h (Day11), 288 h (Day13), 336 h (Day15)last detectable plasma concentration

  Up to 336 h(Day15) post-dose

Secondary Outcomes (7)

• Secondary PK parameters: Tmax

  Up to 336 h(Day15) post-dose

• Secondary PK parameters: T1/2

  Up to 336 h(Day15) post-dose

• Secondary PK parameters: Vz/F

  Up to 336 h(Day15) post-dose

• Secondary PK parameters: CL/F

  Up to 336 h(Day15) post-dose

• Secondary PK parameters: λz

  Up to 336 h(Day15) post-dose

Study Arms (3)

Group A

EXPERIMENTAL

Subjects with mild renal insufficiency (CKD stage 2, GFR: 60-89 mL/min)

Drug: PB119

Group B

EXPERIMENTAL

Subjects with moderate renal insufficiency (CKD stage 3, GFR: 30-59 mL/min)

Drug: PB119

Group C

EXPERIMENTAL

Subjects with normal renal function (GFR: ≥ 90 and \< 130 mL/min)

Drug: PB119

Interventions

PB119 DRUG

Each subject received only one dose of study drug during the study period. After completing the pre-dose procedure on the morning of the first day of the study, the subjects were given a subcutaneous injection of PB-119 0.3 mL (150 μg) once in the abdomen by the study nurse. The actual time of administration will be recorded in the subject's eCRF. Subjects should remain on an empty stomach for at least 10 hours prior to administration.

Group A; Group B; Group C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects included in this study must meet all of the following criteria:
• Subjects who voluntarily sign the informed consent form (ICF) before the commencement of relevant activities of this study, can understand the procedures and methods of this study, and are willing to strictly abide by the clinical study protocol to complete this study;
• Male subjects: Male subjects should voluntarily take effective contraceptive measures, and should not donate sperm from the screening period to 90 days after the administration of the study drug
• Female subjects must meet one of the following conditions:
• Non-fertile women
• Fertile women should voluntarily take effective contraceptive measures from the screening period to 90 days after the administration of the study drug;
• According to the judgment of the investigators, the subject's physical examination, vital signs examination, 12 lead ECG examination and laboratory examination indicators are suitable for participating in this study;
• Subjects in the renal insufficiency group must also meet the following criteria:
• Male or female subjects aged between 18 and 75 years old;
• The weight of male subjects should not be less than 50 kg and that of female subjects should not be less than 45 kg. BMI should be between 18 and 30 kg/m2 (including both end values);
• Subjects with a diagnosis of chronic (\> 3 months) and stable (no acute exacerbation due to renal function aggravated within 1 month before screening) renal injury, and a GFR measured during the screening period in line with 60 89 mL/min (mild renal insufficiency in group A) or 30-59 mL/min (moderate renal insufficiency in group B). Renal function evaluated by individual GFR converted from eGFR calculated according to the CKD-EPI formula;
• Subjects in the normal renal function group must also meet the following criteria:
• Male or female subjects aged between 18 and 75 years old, which should be matched with age (±10 years) and gender of subjects in the renal insufficiency group;
• The weight of male subjects should not be less than 50 kg and that of female subjects should not be less than 45 kg. BMI should be between 18 and 30 kg/m2 (including both end values), which should be matched with BMI (± 15%) of subjects in renal insufficiency group;
• The GFR of subjects with normal renal function should be ≥ 90 and \< 130 mL/min (estimated by CKD-EPI formula).

You may not qualify if:

• All subjects will not be included in this study if they meet any of the following criteria:
• Those with allergic constitution or allergic to any component in PB-119;
• Those with previous medical history or family history of Medullary thyroid cancer (MTC) or Multiple endocrine adenomatosis type 2 (MEN2), or serum calcitonin ≥ 50 pg/mL at screening;
• Those with serum amylase or lipase \>3 × upper limit of normal (ULN) during the screening period or baseline period or subjects with previous diagnosis of acute/chronic pancreatitis;
• Those who had severe gastrointestinal diseases (such as active ulcer, gastroparesis, obstruction pyloric, inflammatory bowel disease, etc.) or underwent gastrointestinal surgery or long-term use of drugs directly affecting gastrointestinal peristalsis due to chronic gastrointestinal diseases within 6 months before screening or during the baseline period are not suitable to participate in this clinical study according to the evaluation of the investigators;
• Those with any type of treated or untreated malignancy (whether cured or not) within 5 years before screening or during the baseline period (except basal cell carcinoma of the skin);
• Those who have major diseases or surgery within 4 weeks before administration, or those who are expected to be hospitalized due to surgery or other reasons during the study period;
• Those with a history of drug abuse or a positive urine drug screening test within 5 years before screening;
• Those who smoked more than 10 cigarettes per day on average within 3 months before screening;
• Those with an average weekly alcohol intake of more than 14 units (female subjects) or 21 units (male subjects) (1 unit of alcohol is equivalent to 284 mL of beer, 1 glass of 125 mL of wine or 25 mL of spirits) in the 3 months prior to screening or who ingested any alcohol-containing products within 48 hours prior to administration, or those with a positive breath alcohol test;
• Clinical investigators who have participated in any drug or medical device within 3 months before screening (subject to administration);
• Those who donated blood (or lost blood) ≥ 400 mL or received blood products within 3 months before screening;
• Those with acute hepatitis, chronic liver disease, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 × ULN and total bilirubin \> 2 × ULN during the screening period or baseline period;
• Those who are positive for any of the hepatitis B surface antigen (HBsAg), hepatitis C virus antibody, human immunodeficiency virus (HIV) antibody, and Treponema pallidum antibody according to the local diagnostic test;
• Female subjects with positive pregnancy test results during the screening period or baseline period;

Sponsors & Collaborators

• PegBio Co., Ltd.: lead

Study Sites (1)

Jia Miao

Chengdu, Sichuan, China

Location

Study Officials

• Jia Miao, MD,PhD

  West China Hospital

  PRINCIPAL INVESTIGATOR

• Ping Fu, MD,PhD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Du, MD,PhD

CONTACT

+8618911797119; ying.du@pegbio.com

Michael Xu, MD,PhD

CONTACT

+86-512-62956129; michael.xu@pegbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2022
• First Posted: April 14, 2022
• Study Start: May 1, 2022
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: April 14, 2022

Record last verified: 2022-04

Locations

CN (1)