Pharmacodynamics and Pharmacokinetics of 3 New Developed Coated Glucose Beads in 20 Obese Healthy Subjects

NCT05713773 | Completed Phase 1 DMC

• 1 other identifier: 017B19
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This single-dose, randomized, open label, five-treatment, five-period, five-sequence crossover study was performed to assess pharmacodynamics (PD) and pharmacokinetics (PK) of three new developed coated Glucose beads formulations (containing glucose (8 g) and caffeine), one coated Glucose beads formulation (containing glucose (8 g)) and one uncoated Glucose beads formulation (containing Glucose (8 g) and caffeine) after single-dose administration (fasting conditions) in 20 obese healthy subjects. After an overnight fasting of at least 10 hours the subjects were administered either glucose (8 g) or glucose (8 g) and caffeine starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position. At least 3 days wash-out period was kept between each treatment periods.

Conditions

Metabolic Syndrome; Obesity

Outcome Measures

Primary Outcomes (9)

• GLP-1

  Area under the plasma concentration-time curve (AUC(0-t))

  Pre-dose (-1.0 h, -0.5 h and 0 h) 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

  AUC(1.5h-6h)

  Pre-dose (-1.0 h, -0.5 h and 0 h) 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

  Adjusted area under the plasma concentration-time cur (AUCadj(1.5h-6h))

  Pre-dose (-1.0 h, -0.5 h and 0 h) 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

  Maximum plasma concentration (Cmax(0-t))

  Pre-dose (-1.0 h, -0.5 h and 0 h) 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

  Cmax(1.5h-6h)

  Pre-dose (-1.0 h, -0.5 h and 0 h) 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

  Cmax,adj(1.5h-6h)

  Pre-dose (-1.0 h, -0.5 h and 0 h) 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

  time to reach maximum plasma concentration (tmax(0-t))

  Pre-dose (-1.0 h, -0.5 h and 0 h) 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

  tmax(1.5h-6h)

  Pre-dose (-1.0 h, -0.5 h and 0 h) 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

  Duration of time during the concentration in the plasma concentration-time curve exceeds at least 50 % of Cmax(1.5h-6h)

  Pre-dose (-1.0 h, -0.5 h and 0 h) 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 (14)

• Pharmacokinetics of Caffeine

  Pre-dose (1.0 h, 0.5 h and 0 h) 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

• Pharmacokinetics of Caffeine

  Pre-dose (1.0 h, 0.5 h and 0 h) 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

• Pharmacokinetics of Caffeine

  Pre-dose (1.0 h, 0.5 h and 0 h) 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

• Pharmacokinetics of Caffeine

  Pre-dose (1.0 h, 0.5 h and 0 h) 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

• Pharmacokinetics of Glucose

  Venous blood glucose measurement at the prescribed times pre-dose (-1.0 h, 0 h) 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

Study Arms (5)

Test product 1 (T1)

ACTIVE COMPARATOR

Aphaia Pharma (APH)-001A: glucose coated beads containing 8 g glucose and caffeine anhydrous

Drug: coated beads glucose (8 g) and caffeine anhydrous

Test product 2 (T2)

ACTIVE COMPARATOR

APH-001B: glucose coated beads containing 8 g glucose and caffeine anhydrous

Drug: coated beads glucose (8 g) and caffeine anhydrous

Test product 3 (T3)

ACTIVE COMPARATOR

APH-001C: glucose coated beads containing 8 g glucose and caffeine anhydrous

Drug: coated beads glucose (8 g) and caffeine anhydrous

Test product 4 (T4)

ACTIVE COMPARATOR

APH-001D: glucose coated beads containing 8 g glucose

Drug: coated beads glucose (8 g)

Test product 5 (T5)

ACTIVE COMPARATOR

APH-001E: uncoated beads containing 8 g glucose and caffeine anhydrous

Drug: uncoated beads glucose (8 g) and caffeine anhydrous

Interventions

coated beads glucose (8 g) and caffeine anhydrous DRUG

After an overnight fasting of about 10 hours the subjects were administered either glucose (8 g) or glucose (8 g) and caffeine starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position on Day 1.

Also known as: APH-001A

Test product 1 (T1)

coated beads glucose (8 g) DRUG

After an overnight fasting of about 10 hours the subjects were administered glucose (8 g) starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position on Day 1.

Also known as: APH-001D

Test product 4 (T4)

uncoated beads glucose (8 g) and caffeine anhydrous DRUG

After an overnight fasting of about 10 hours the subjects were administered either glucose (8 g) or glucose (8 g) and caffeine starting at 8:00 (time 0; administration time was staggered beginning at 8:00 for the first group of subjects) in sitting position on Day 1.

Also known as: APH-001E

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 stabilized 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 gastrointestinal (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
• Non-smokers or mild to moderate smokers (less or equal 10 cigarettes daily)

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, prazole)
• Tea, coffee or other caffeine containing beverage drinkers (more than 0.4 L per day)
• 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)
• Clinically significant illness or surgery within 4 weeks prior to dosing
• Less than 14 days after last acute disease
• Volunteers liable to orthostatic dysregulation, fainting, or blackouts
• Donation or loss of blood equal to or exceeding 500 ml during 90 days before the first administration of investigational product
• Participation in another study with an experimental drug within at least 3 months (or within five elimination half-lives of the previous experimental drug, whichever is longer) before the first administration of investigational product

Sponsors & Collaborators

• Aphaia Pharma US LLC: lead
• ACC GmbH Analytical Clinical Concepts, Germany: collaborator
• Nova-Clin Medical Research Center S.R.L., Romania: collaborator
• BioClinica, Inc.: collaborator
• Galephar Pharmaceutical Research (PR), Inc, Puerto Rico: collaborator

Study Sites (1)

Nova-Clin Medical Research Center S.R.L.,

Timișoara, 300696, Romania

Location

MeSH Terms

Conditions

Metabolic Syndrome; Obesity

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Carmen Vizman, Doctor

  Aphaia Pharma AG

  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: single-dose, randomized, open label, five-treatment, five-period, five-sequence crossover, at one study site

Study Record Dates

• First Submitted: January 19, 2023
• First Posted: February 6, 2023
• Study Start: October 25, 2019
• Primary Completion: December 3, 2019
• Study Completion: December 3, 2019
• Last Updated: February 6, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

RO (1)