2-HOBA: Initial Evaluation in Humans (2-HOBA)

• ClinicalTrials.gov Identifier: NCT03176940
• Recruitment Status: Completed
• First Posted: June 6, 2017
• Last Update Posted: June 4, 2018
• Sponsor: Metabolic Technologies Inc.
• Collaborators: Vanderbilt University; National Institute on Aging (NIA)
• Information provided by (Responsible Party): John Rathmacher, PhD, Metabolic Technologies Inc.

Study Description

Brief Summary:

The purpose of this study is to evaluate the administration of single doses of 2-HOBA in humans, with an escalation of doses that begins with the calculated Maximum Recommended Starting Dose. This evaluation will assess tolerability to oral administration of 2-HOBA, obtain pharmacokinetic data, characterize the 2-HOBA metabolic pathways, and determine the relation of dose to prevention of formation of bi-functional electrophile adducts in blood. Characterization of the metabolic fate of 2-HOBA will be supported by investigations that evaluate metabolism in microsomes and cells.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers	Dietary Supplement: 2-HOBA	Not Applicable

Detailed Description:

Consenting volunteers of at least 18 years old with no morbidity, including males, and females who are not pregnant will be recruited for the study. A maximum of 28 volunteers may be enrolled with a reasonable sampling of ethnicities from the Nashville area, and an effort will be made to recruit equal numbers of males and females. Additionally, an effort will be made to study as old a population as possible and to recruit relatively similar age groups for males and females. All volunteers will be admitted to the Vanderbilt Clinical Research Center (CRC) as inpatients.

A complete health history and physical examination will be conducted by a physician. Volunteers will be asked to collect and bring their first morning voided urine for baseline urinalysis. An EKG, baseline blood analysis, vital signs, and questions about feelings and adverse events will be asked prior to supplement administration. All tests will be repeated at various intervals throughout the 24-hour study period. A physician will oversee all clinical aspects of the study and will be responsible for all trial-related medical decisions. Pharmacokinetics will be studied through the blood analyses at intervals throughout the study and 24-hour urine collection after administration of the supplement.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: The 3+3 design will be employed for this trial. At least 3 volunteers will be studied at each dose level and evaluated for adverse effects. If 0 of 3 volunteers experiences adverse events (AE), the dose is escalated. If 1 of 3 volunteers experiences an AE, 3 additional volunteers are treated. If none of the additional volunteers develop an AE, the dose is escalated, otherwise escalation ceases. If 2 of 3 or 2 of 6 volunteers experience an AE, the maximum tolerated dose (MTD) has been exceeded.
• Masking: Double (Participant, Care Provider)
• Masking Description: The dietary supplement will be delivered to the Clinical Research Center by the Investigational Pharmacy at Vanderbilt University Medical Center. Staff nurses and participants will be blinded to the capsule dosage content.
• Primary Purpose: Basic Science
• Official Title: 2-Hydroxybenzylamine: Initial Evaluation in Humans
• Actual Study Start Date: August 2, 2017
• Actual Primary Completion Date: March 31, 2018
• Actual Study Completion Date: April 30, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: 2-HOBA first dose; Dose escalation studies in humans: 50mg dose	Dietary Supplement: 2-HOBA; 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate; Other Name: 2-Hydroxylbenzylamine
Experimental: 2-HOBA second dose; Dose escalation studies in humans: 100mg dose	Dietary Supplement: 2-HOBA; 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate; Other Name: 2-Hydroxylbenzylamine
Experimental: 2-HOBA third dose; Dose escalation studies in humans: 200mg dose	Dietary Supplement: 2-HOBA; 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate; Other Name: 2-Hydroxylbenzylamine
Experimental: 2-HOBA fourth dose; Dose escalation studies in humans: 330mg dose	Dietary Supplement: 2-HOBA; 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate; Other Name: 2-Hydroxylbenzylamine
Experimental: 2-HOBA fifth dose; Dose escalation studies in humans: 550mg dose	Dietary Supplement: 2-HOBA; 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate; Other Name: 2-Hydroxylbenzylamine
Experimental: 2-HOBA sixth dose; Dose escalation studies in humans: 825mg dose	Dietary Supplement: 2-HOBA; 2-HOBA is a compound found in buckwheat and is given as 2-HOBA acetate; Other Name: 2-Hydroxylbenzylamine

Outcome Measures

Primary Outcome Measures :

1. Dose Tolerability [ Time Frame: 24 hours ]

   Tolerability will be assessed by occurrence of Adverse Events (AEs). If AEs occur in 2 out of 6 volunteers, the dose will be declared not tolerated and the previous dose with no AEs will be declared maximum tolerable dose.

   AEs < 2: dose is tolerated AEs ≥ 2: dose is not tolerated

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy individuals older than 18;
• Males and females who are not pregnant at the time of the study; and
• Not taking any medication 2 weeks prior to and during the study.

Exclusion Criteria:

• Inability to give informed consent;
• Diseases that could manifest symptoms or signs that would confound interpretation of the relation between drug action and potential adverse effects;
• Diseases that could manifest morbidity;
• Known cardiac disease, kidney disease, or hepatic dysfunction;
• The need to discontinue any drug that is administered as standard of care treatment; and
• Unwillingness or inability to use approved birth-control methods.

Contacts and Locations

Locations

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Metabolic Technologies Inc.

Vanderbilt University

National Institute on Aging (NIA)

Investigators

• Principal Investigator: John A Rathmacher, PhD; Metabolic Technologies Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pitchford LM, Rathmacher JA, Fuller JC Jr, Daniels JS, Morrison RD, Akers WS, Abumrad NN, Amarnath V, Currey PM, Roberts LJ, Oates JA, Boutaud O. First-in-human study assessing safety, tolerability, and pharmacokinetics of 2-hydroxybenzylamine acetate, a selective dicarbonyl electrophile scavenger, in healthy volunteers. BMC Pharmacol Toxicol. 2019 Jan 5;20(1):1. doi: 10.1186/s40360-018-0281-7.

• Responsible Party: John Rathmacher, PhD, Director of Clinical Research, Metabolic Technologies Inc.
• ClinicalTrials.gov Identifier: NCT03176940
• Other Study ID Numbers: 161861; R44AG055184 ( U.S. NIH Grant/Contract )
• First Posted: June 6, 2017
• Last Update Posted: June 4, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by John Rathmacher, PhD, Metabolic Technologies Inc.:

Escalating Dosage