Dose-finding of PB-119 Administered Subcutaneously Once Weekly Versus Placebo in Subjects With Type 2 Diabetes

NCT ID: NCT03604419

Last Updated: 2020-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-13
• Study Completion Date: 2019-07-23

Brief Summary

A phase 2, multicenter study to evaluate the efficacy and safety of twelve once weekly subcutaneous doses of PB-119 to patients with type 2 diabetes mellitus (T2DM) not well-controlled by metformin mono therapy.

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, parallel dose cohort, multiple dose study to evaluate the efficacy, safety, and tolerability of different doses of PB-119 to patients with T2DM not well-controlled by metformin monotherapy. Patients will be assessed for eligibility over a 2 week screening period prior to a 4-week run-in period and a 12-week double-blind treatment period.A phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel dose cohort study to evaluate the efficacy and safety of twelve once weekly subcutaneous doses of PB-119 to patients with type 2 diabetes mellitus (T2DM) not well-controlled by metformin monotherapy The eligible patients will be randomized to 1 of 3 dose cohorts (A, B, or C). Each patient will subsequently be randomized within the designated cohort to 1) active drug or placebo at a 3:1 active drug:placebo ratio and 2) exclusion from or inclusion in the pharmacokinetic (PK) blood sample collection subgroup at a 3:1 excluded:included ratio

Conditions

Type 2 Diabetes Mellitus (T2DM)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

PB-119 100 μg

PB-119 100 μg subcutaneous (SC) once weekly (QW) + Metformin oral (p.o.) Glucophage® (stable dosage)

Group Type: EXPERIMENTAL

PB-119 150 μg+ Glucophage®

Intervention Type: DRUG

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

PB-119 200 μg+ Glucophage®

Intervention Type: DRUG

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

PB-119 placebo + Glucophage®

Intervention Type: DRUG

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

PB-119 150 μg

PB-119 150 μg SC QW + Metformin oral (p.o.) Glucophage® (stable dosage)

Group Type: EXPERIMENTAL

PB-119 100 μg+ Glucophage®

Intervention Type: DRUG

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

PB-119 200 μg+ Glucophage®

Intervention Type: DRUG

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

PB-119 placebo + Glucophage®

Intervention Type: DRUG

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

PB-119 200 μg

PB-119 200 μg SC QW + Metformin oral (p.o.) Glucophage® (stable dosage)

Group Type: EXPERIMENTAL

PB-119 100 μg+ Glucophage®

Intervention Type: DRUG

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

PB-119 150 μg+ Glucophage®

Intervention Type: DRUG

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

PB-119 placebo + Glucophage®

Intervention Type: DRUG

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

PB-119 Placebo

PB-119 Placebo SC QW + Metformin oral (p.o.) Glucophage® (stable dosage)

Group Type: PLACEBO_COMPARATOR

PB-119 100 μg+ Glucophage®

Intervention Type: DRUG

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

PB-119 150 μg+ Glucophage®

Intervention Type: DRUG

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

PB-119 200 μg+ Glucophage®

Intervention Type: DRUG

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

Interventions

PB-119 100 μg+ Glucophage®

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

Intervention Type: DRUG

PB-119 150 μg+ Glucophage®

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

Intervention Type: DRUG

PB-119 200 μg+ Glucophage®

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

Intervention Type: DRUG

PB-119 placebo + Glucophage®

Each patient will subsequently be randomized within the designated cohort to active drug or placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients in whom T2DM has been diagnosed according to 2018 American Diabetes Association T2DM diagnostic criteria, have made lifestyle modifications (ie, diet and exercise) for at least 3 months prior to Screening, and have been taking metformin for at least 3 months before Screening with a stable dosage for at least 8 weeks (stable dosage is defined as metformin dosage ≥1500 mg/day or maximum tolerated dose).

2. Males and/or females between the ages of ≥18 and ≤70 years at Screening

3. HbA1c ≥7.5% and ≤11% at Screening and at Week -1, Visit 3.1;

4. FPG ≥126 and ≤240 mg/dL (≥7.0 and ≤13.3 mmol/L) at Screening and at Week -1, Visit 3.1;

5. Body mass index (BMI) ≥18.5 and ≤40.0 kg/m2 at Screening, with inclusion of patients with BMIs at the lower end of the range enrolled into the study to enable comparisons across BMI range;

Exclusion Criteria

1. Medical history or current diagnosis of:

1. Type 1 diabetes mellitus, diabetes caused by pancreas injury or by other diseases (like acromegaly or Cushing syndrome);

2. Diabetes acute complication, like ketoacidosis or hyperosmolar coma;

3. Diagnosed proliferative retinopathy;

4. 3 instances of severe hypoglycemia (events during which the patient required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions; episodes may be associated with sufficient neuroglycopenia to have induced seizure or coma) in the 6 months prior to Screening;

5. Significant vascular disease;

2. Current/ongoing diagnosis of any type of malignant tumor or evidence of recurrence in the 6 months prior to Screening (patients who have been stable for ≥6 months or those who have had basal or squamous cell skin cancers removed and have no evidence of recurrence will not be excluded). Patients with a medical history of any other type of cancer in the last 5 years prior to Screening will be excluded;

3. Severe cardiovascular diseases occurring within 6 months prior to Screening (eg, congestive heart disease, myocardial infarction, acute coronary syndrome, apoplexy, transient ischemic attack);

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Covance

INDUSTRY

Sponsor Role: collaborator

PegBio Co., Ltd.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clinical Pharmacology of Miami

Miami, Florida, United States

Countries

United States

References

Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.

Reference Type: DERIVED

PMID: 30957581 (View on PubMed)

Other Identifiers

PB119202

Identifier Type: -

Identifier Source: org_study_id