A Clinical Trial to Assess the Pharmacokinetic Profile of Propylene Glycol (PG) in Healthy Adults Following PG Exposure

Official title

An Open-label, Dose-escalation Clinical Trial to Assess the Pharmacokinetic Profile of Propylene Glycol (PG) in Healthy Adults Following PG Exposure

Overview

The goal of this clinical trial is to determine the translation of propylene glycol (PG) exposure in beverages to circulating PG levels to better understand the margin of safety in healthy participants. The main question it aims to answer is what is the maximum concentration (Cmax) of propylene glycol (PG) in serum following consumption of one, two, or three PG-containing beverages? Participants will be asked to: * Consume 1x, 2x, and 3x 12oz of PG-containing beverage * Have their blood drawn * Complete urine pregnancy testing if of childbearing potential * Complete a study diary and record their food and beverage consumption * Have their vital signs and oxygen measurements taken

Interventions

• Other Propylene glycol
  At Visits 2, 4, and 6, participants will consume 1X, 2X, and 3X 12 oz of a PG-containing beverage (in bottle format) with standardized meals in the presence of the study staff over the course of the dosing day. Participants will consume the beverage and standardized meal within 15 minutes. The only beverage allowed during the visit - other than the intent-to-treat beverage - will be water.

Primary outcome measures

• The maximum concentration of propylene glycol in serum [Time frame: From pre-dose through 24 hours post-dose.]

Secondary outcome measures (9)

• Serum PG Levels [Time frame: Baseline (pre-dose) at each dosing visit]
• Tmax [Time frame: From pre-dose through 24 hours post-dose]
• Area Under the Curve (AUC0-24hrs) [Time frame: From pre-dose through 24 hours post-dose]
• AUC0-∞ [Time frame: From pre-dose through 24 hours post-dose]
• Terminal elimination half-life (t1/2) [Time frame: From pre-dose through 24 hours post-dose]
• Measured and calculated osmolality [Time frame: Assessed at baseline (0 hour) and at 0.5 hour, 1 hour, 1.5 hours, 2 hours, 4 hours, 5 hours, 6 hours, 8 hours, 9 hours, 12 hours, and 24 hours post-dose]
• Blood osmolal gap [Time frame: Assessed at baseline (0 hour) and at 0.5 hour, 1 hour, 1.5 hours, 2 hours, 4 hours, 5 hours, 6 hours, 8 hours, 9 hours, 12 hours, and 24 hours post-dose]
• Serum lactate concentration [Time frame: Assessed at baseline (0 hour) and at 0.5 hour, 1 hour, 1.5 hours, 2 hours, 4 hours, 5 hours, 6 hours, 8 hours, 9 hours, 12 hours, and 24 hours post-dose]
• pyruvate concentration [Time frame: Assessed at baseline (0 hour) and at 0.5 hour, 1 hour, 1.5 hours, 2 hours, 4 hours, 5 hours, 6 hours, 8 hours, 9 hours, 12 hours, and 24 hours post-dose]

Eligibility criteria

Inclusion criteria

• Males and females 18 years and older
• Body Mass Index (BMI) between 18.5 to 29.9 kg/m2
• Females not of child-bearing potential, defined as those who have undergone a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, bilateral tubal ligation, complete endometrial ablation) or have been post-menopausal for at least 1 year prior to screening Or,

Individuals of child-bearing potential must have a negative baseline urine pregnancy test and agree to use a medically approved method of birth control for the duration of the study. All hormonal birth control must have been in use for a minimum of three months. Acceptable methods of birth control include:

• Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo-Provera, Lunelle), or hormone implant (Nexplanon)
• Double-barrier method
• Intrauterine devices
• Non-heterosexual lifestyle and agrees to use contraception if planning on changing to heterosexual partner(s)
• Vasectomy of partner at least 6 months prior to screening
• Abstinence and agrees to use contraception if planning on becoming sexually active during the study
• Agrees to refrain from vigorous physical activity and alcohol consumption 24 hours prior to dosing day (i.e., Day 1 of each study period which corresponds to Visits 2, 4, 6) and Day 2 of each study period
• Willingness to complete diaries, food records, and to complete all clinic visits
• Agrees to maintain current lifestyle habits (diet, physical activity, medications, supplements, and sleep) as much as possible throughout the study
• Provided voluntary, written, informed consent to participate in the study
• Healthy as determined by medical history and laboratory results as assessed by the Qualified Investigator (QI)

Exclusion criteria

• Individuals who are pregnant, breast feeding, or planning to become pregnant during the study
• Allergy, sensitivity, or intolerance, preventing consumption of investigational product ingredients and standardized meal
• Individuals with alcohol dehydrogenase deficiency as assessed by the QI
• Poor venous access as assessed by the QI
• History of or current diagnosis with kidney and/or liver diseases as assessed by the QI on a case-by case basis, with the exception of history of kidney stones in participants who are symptom free for 6 months
• Significant cardiovascular event in the past 6 months. (Participants with no significant cardiovascular event on stable medication may be included after assessment by the QI on a case-by-case basis.)
• Self-reported confirmation of any significant neuropsychological condition (e.g., Schizophrenia, bipolar disorder, post-traumatic stress disorder, brain injury, neurodegenerative disease, infections, insomnia, anxiety, depression, epileptic or other seizure-related disorders) as assessed by the QI
• Unstable metabolic disease or chronic diseases as assessed by the QI
• Current or history of any significant diseases of the gastrointestinal tract as assessed by the QI
• Unstable hypertension. Treatment on a stable dose of medication for at least 3 months will be considered by the QI (See Section 7.3)
• Self-reported confirmation of current or pre-existing thyroid condition. Treatment on a stable dose of medication for at least 3 months will be considered by the QI
• Major surgery in the past 3 months or individuals who have planned surgery during the course of the study. (Participants with minor surgery will be considered on a case-by-case basis by the QI.)
• Cancer, except skin basal cell carcinoma completely excised with no chemotherapy or radiation with a follow up that is negative. Volunteers with cancer in full remission for more than five years after diagnosis are acceptable.
• Individuals with an autoimmune disease or are immune compromised as assessed by the QI.
• Self-reported confirmation of a HIV-, Hepatitis B- and/or C-positive diagnosis as assessed by the QI
• Self-reported confirmation of blood/bleeding disorders as assessed by the QI
• Use of prescribed cannabinoid products
• Chronic use of cannabinoid products (>2 times/week). Occasional users will be required to washout and abstain for the duration of the study period
• Regular use of e-cigarettes, tobacco or nicotine products in the past six months, as assessed by the QI. Occasional users will be required to washout (1 month) and abstain for the duration of the study period.
• Alcohol intake average of >1 standard drinks per day as assessed by the QI
• Alcohol or drug abuse within the last 12 months
• Current use of prescribed and/or over-the-counter (OTC) medications, supplements, and/or consumption of food/drinks that may impact the safety of the investigational product (Sections 7.3.1 and 7.3.2)
• Clinically significant abnormal laboratory results at screening as assessed by the QI
• Blood donation 30 days prior to baseline, during the study, or a planned donation within 30 days of the last study visit
• Participation in other clinical research studies 30 days prior to baseline, as assessed by the QI
• Individuals who are unable to give informed consent
• Any other condition or lifestyle factor, that, in the opinion of the QI, may adversely affect the participant's ability to complete the study or its measures or pose significant risk to the participant

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Basic science

Study locations

Canada · 1 center

• KGK Science Inc. — London

Identifiers

NCT: NCT07644169 · 26ABAKC01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗