Pharmacodynamics and Pharmacokinetics of Different Glucose Bead Formulations in Obese Healthy Subjects

NCT05737927 | Completed Phase 1 DMC

• 1 other identifier: 008B20
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical study was to assess pharmacodynamics (PD) and pharmacokinetics (PK) of different Glucose beads formulations in obese healthy subjects under fasting condition. The study was designed in 2 parts. Part 1 (single-dose) of the study was randomized, open label, five-treatment, five-period, five-sequence, crossover and single-centric. Treatment arms were three dosages of a coated Glucose beads formulation (47% w/w glucose/bead; 8 g \[T1\], 12 g \[T2\] and 16 g glucose \[T3\]), one uncoated Glucose beads formulation (47% w/w glucose/bead; 12 g glucose \[T4\]) and one coated Glucose beads formulation (60% w/w glucose/bead;12 g glucose \[T5\]). Part 2 (multiple-dose) of the study was open label, one-treatment, one-period and single-centric. Treatment arm was coated Glucose beads formulation (12 g glucose \[T2\]).

Conditions

Obese

Outcome Measures

Primary Outcomes (11)

• GLP-1

  Part 1: Area under the plasma concentration-time curve from the first time point zero to the last measured concentration (AUC\[0-t\])

  Pre-dose (-1.0 hour, -0.5 hour and 0 hour [within 5 minutes]) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.

• GLP-1

  Part 1: Area under the plasma concentration-time curve from the time point 1.5 hours to 8 hours (AUC\[1.5 hours-8 hours\])

  Pre-dose (-1.0 hour, -0.5 hour and 0 hour [within 5 minutes]) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.

• GLP-1

  Part 1: Adjusted area under the plasma concentration-time curve from the time point 1.5 hours to 8 hours (AUCadj.\[1.5 hours-8 hours\])

  Pre-dose (-1.0 hour, -0.5 hour and 0 hour [within 5 minutes]) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.

• GLP-1

  Part 1: Maximum plasma concentration (Cmax\[0-t\])

  Pre-dose (-1.0 hour, -0.5 hour and 0 hour [within 5 minutes]) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.

• GLP-1

  Part 1: Maximum plasma concentration between the time point 1.5 hours to 8 hours (Cmax\[1.5 hours-8 hours\])

  Pre-dose (-1.0 hour, -0.5 hour and 0 hour [within 5 minutes]) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.

• GLP-1

  Part 1: Adjusted maximum plasma concentration between the time point 1.5 hours to 8 hours (Cmax,adj.\[1.5 hours-8 hours\])

  Pre-dose (-1.0 hour, -0.5 hour and 0 hour [within 5 minutes]) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.

• GLP-1

  Part 1: Time of maximum plasma concentration (tmax\[0-t\])

  Pre-dose (-1.0 hour, -0.5 hour and 0 hour [within 5 minutes]) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.

• GLP-1

  Part 1: Time of maximum plasma concentration between the time point 1.5 hours to 8 hours (tmax\[1.5 hours-8 hours\])

  Pre-dose (-1.0 hour, -0.5 hour and 0 hour [within 5 minutes]) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.

• GLP-1

  Part 2: Area under the plasma concentration-time curve during a dosage interval at steady state (AUC\[0-τ\])

  Day 1-3:- pre-dose (-1.0 hour, -0.5 hour and 0 hour). Day 4:- Pre-dose (-1.0 hour, -0.5 hour and 0 hour [within 5 minutes]) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.

• GLP-1

  Part 2: Maximum plasma concentration at steady state (Cmax,ss)

  Day 1-3:- pre-dose (-1.0 hour, -0.5 hour and 0 hour). Day 4:- Pre-dose (-1.0 hour, -0.5 hour and 0 hour [within 5 minutes]) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.

• GLP-1

  Part 2: Concentration at the end of the dosing interval at steady state (Cτ,ss)

  Day 1-3:- pre-dose (-1.0 hour, -0.5 hour and 0 hour). Day 4:- Pre-dose (-1.0 hour, -0.5 hour and 0 hour [within 5 minutes]) and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0 and 10.0 hours after investigational product administration.

Secondary Outcomes (6)

• Glucose levels

  Pre-dose (-1.0 hour, 0 hour [within 5 minutes]) and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0 and 10.0 hours after investigational product administration.

• Glucose levels

  Pre-dose (-1.0 hour, 0 hour [within 5 minutes]) and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0 and 10.0 hours after investigational product administration.

• Glucose levels

  Day 1- Day 3:- Pre-dose (3 samples). Day 4:- Pre-dose (-1.0 hour, 0 hour [within 5 minutes]) and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0 and 10.0 hours after investigational product administration.

• Glucose levels

  Day 1- Day 3:- Pre-dose (3 samples). Day 4:- Pre-dose (-1.0 hour, 0 hour [within 5 minutes]) and 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0 and 10.0 hours after investigational product administration.

• Visual analogue scale appetite

  Pre-dose (0 hour) and 2, 3, 4, 5, 6, 8 and 10 hours after investigational product administration.

Study Arms (6)

SINGLE DOSE- TEST PRODUCT 1 (T1)

ACTIVE COMPARATOR

Oral coated beads 8 g glucose (content glucose/bead 47% w/w)

Drug: Glucose 8 g coated beads (47% w/w)

SINGLE DOSE- TEST PRODUCT 2 (T2)

ACTIVE COMPARATOR

Oral coated beads 12 g glucose (content glucose/bead 47% w/w)

Drug: Glucose 12 g coated beads (47% w/w)

SINGLE DOSE- TEST PRODUCT 3 (T3)

ACTIVE COMPARATOR

Oral coated beads 16 g glucose (content glucose/bead 47% w/w)

Drug: Glucose 16 g coated beads (47% w/w)

SINGLE DOSE- TEST PRODUCT 4 (T4)

ACTIVE COMPARATOR

Oral uncoated beads 12 g glucose

Drug: Glucose 12 g uncoated beads

SINGLE DOSE- TEST PRODUCT 5 (T5)

ACTIVE COMPARATOR

Oral coated beads 12 g glucose (content glucose/bead 60% w/w)

Drug: Glucose 12 g coated beads (60% w/w)

MULTIPLE DOSE- TEST PRODUCT 2 (T2)

ACTIVE COMPARATOR

Oral coated beads 12 g glucose (content glucose/bead 47% w/w)

Drug: Glucose 12 g coated beads (47% w/w)

Interventions

Glucose 8 g coated beads (47% w/w) DRUG

After an overnight fasting of about 10 hours, the subjects were administered 8 g glucose of the coated Glucose beads formulation starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position.

Also known as: APHD-008

SINGLE DOSE- TEST PRODUCT 1 (T1)

Glucose 12 g coated beads (47% w/w) DRUG

After an overnight fasting of about 10 hours, the subjects were administered 12 g glucose of the coated Glucose beads formulation starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position.

Also known as: APHD-012

SINGLE DOSE- TEST PRODUCT 2 (T2)

Glucose 16 g coated beads (47% w/w) DRUG

After an overnight fasting of about 10 hours, the subjects were administered 16 g glucose of the coated Glucose beads formulation starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position.

Also known as: APHD-016

SINGLE DOSE- TEST PRODUCT 3 (T3)

Glucose 12 g uncoated beads DRUG

After an overnight fasting of about 10 hours, the subjects were administered the uncoated Glucose beads formulation containing 12 g glucose starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position.

Also known as: APHD-012P

SINGLE DOSE- TEST PRODUCT 4 (T4)

Glucose 12 g coated beads (60% w/w) DRUG

After an overnight fasting of about 10 hours, the subjects were administered the coated Glucose beads formulation (60 % w/w glucose/bead; 12 g glucose) starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position.

Also known as: APHD-012-60

SINGLE DOSE- TEST PRODUCT 5 (T5)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy obese, Caucasian, male and female subjects 18 - 55 years of age
• Body mass index within the range of \> 30.0 kg/m2
• Waist circumference: men \> 102 cm
• women \> 88 cm
• Female subjects of childbearing potential agree to undergo pregnancy tests and to use an appropriate method of contraception (i.e. oral contraceptive steroids, intrauterine device, barrier method)
• Findings within the range of clinical acceptability in medical history (or the clinical investigator considers the deviation to be irrelevant for the purpose of the study)
• Findings within the range of clinical acceptability in physical examination (or the clinical investigator considers the deviation to be irrelevant for the purpose of the study)
• Laboratory values within the normal range (or the clinical investigator considers the deviation to be irrelevant for the purpose of the study)
• Normal ECG or abnormalities which the clinical investigator does not consider a disqualification for participation in the study
• Normal vital signs (normal blood pressure and heart rate measured under stabilised conditions at screening visit after at least 5 minutes of rest in sitting position) or abnormalities which the clinical investigator does not consider a disqualification for participation in the study
• Normal GI function, or abnormalities which the clinical investigator does not consider a disqualification for participation in the study
• Willingness to undergo screening and follow-up examinations (i.e. physical examinations and laboratory investigations before and after the treatment periods)
• Ability to comprehend subject information and willingness to sign the informed consent

You may not qualify if:

• Gastrointestinal, hepatic and renal diseases and/or pathological findings, which might interfere with pharmacokinetics and pharmacodynamics of the investigational product
• Established diagnosis of type-1 or type-2 diabetes mellitus
• Treatment with insulin, insulin secretagogues (sulfonylurea derivatives, glinides, GLP-1 agonists (exenatide, lixisenatide, glutides), or thiazolidinediones (glitazones)
• Unexplained rise in blood glucose
• Treatment for constipation (including but not limited to lactulose or any other form of stool softeners, laxatives) or diarrhea (including but not limited to pectins, loperamide etc.) or any other medication known to interfere with gastrointestinal transit time, such as e.g. metoclopramide, opioids, or gastric potential of hydrogen (pH) (including but not limited to antacids, H2-receptor antagonists, prazoles)
• History of hypersensitivity to the investigational product or any related drugs or to any of the excipients
• History or presence of any clinically significant cardiovascular, pulmonary, hepatobiliary, renal, hematological, gastrointestinal, endocrinologic, immunologic, dermatologic, neurological, psychiatric, metabolic, musculoskeletal, or malignant disease, which the clinical investigator does not consider a disqualification for participation in the study
• Known heart failure (Grade I to IV of New York Heart Association classification)
• Significant renal disease, including nephritic syndrome, chronic renal failure (defined as creatinine clearance \< 60 mL/min and serum creatinine \>180 μmol/L)
• Unexplained serum creatine phosphokinase (CPK) \> 3-times the upper limit of normal (ULN).
• Clinically significant abnormal laboratory values
• Clinically significant ECG findings
• Clinically significant vital signs
• Clinically significant illness or surgery within 4 weeks prior to dosing
• Less than 14 days after last acute disease

Sponsors & Collaborators

• Aphaia Pharma US LLC: lead
• NovaClin Medical Research Center S.R.L: collaborator
• ACC GmbH Analytical Clinical Concepts: collaborator
• SC Bioclinica SA: collaborator
• Galephar Pharmaceutical Research (PR), Inc.: collaborator

Study Sites (1)

NovaClin Medical Research Center S.R.L

Timișoara, Romania, 300696, Romania

Location

MeSH Terms

Conditions

Obesity

Interventions

Glucose

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates

Study Officials

• Carmen Vizman

  NovaClin Medical Research Center S.R.L

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Part 1: randomised, open label, five-treatment, five-period, five-sequence, crossover, at one study site Part 2: open label, one-treatment, one-period, at one study site

Study Record Dates

• First Submitted: January 19, 2023
• First Posted: February 21, 2023
• Study Start: September 16, 2020
• Primary Completion: November 9, 2020
• Study Completion: November 9, 2020
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

RO (1)