Mechanistic Investigation Of Intestinal Cytochrome p450 3A4 Following Roux-en-Y Surgery And Its Effect on Plasma Concentrations of Buspirone

NCT02483598 | Terminated Phase 4

• 1 other identifier: bus-000
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is to compare intestinal Cytochrome P450 3A4 (CYP3A4) activity in 9-18 month post weight loss surgery Roux-en-Y Gastric Bypass (RYGB) versus control subjects who have not had a weight loss surgery and are of similar age, gender, body mass index as the gastric bypass group. For this purpose, we will compare post-bariatric surgery patients with control subjects on alterations in systemic exposure of buspirone, a CYP3A4 substrate, when administered with grapefruit juice, a selective intestinal CYP3A4 inhibitor.

Conditions

Gastric Bypass

Keywords

buspirone; pharmacokinetics; Cytochrome P450 3A4

Outcome Measures

Primary Outcomes (1)

• Area-under-the-curve

  The primary aim of this study is to compare the relative difference between the area-under-the-curve (AUC) of buspirone alone (buspirone) with the AUC of buspirone in the presence of grapefruit juice (buspirone + GFJ) in patients who underwent RYGB 9-18 months prior versus a control group of participants who have not undergone bariatric surgery.

  9-18 months following RYGB

Secondary Outcomes (2)

• Composite of pharmacokinetic measures compared between buspirone and buspirone with grapefruit juice in participants who have undergone RYGB and nonsurgical control participants.

  9-18 months following RYGB

• Compare GLP-2 levels between the buspirone and buspirone with grapefruit juice in participants who have undergone RYGB and nonsurgical control participants.

  9-18 months following RYGB

Study Arms (2)

Buspirone

EXPERIMENTAL

Buspirone alone

Drug: Buspirone; Drug: Buspirone and Grapefruit Juice

Buspirone plus grapefruit juice

ACTIVE COMPARATOR

Buspirone plus grapefruit juice

Drug: Buspirone; Drug: Buspirone and Grapefruit Juice

Interventions

Buspirone DRUG

The primary aim of this study is to compare the relative difference between the area-under-the-curve (AUC) of buspirone alone (buspirone) with the AUC of buspirone in the presence of grapefruit juice (buspirone + GFJ) in patients who underwent RYGB 9-18 months prior versus a control group of participants who have not undergone bariatric surgery.

Buspirone; Buspirone plus grapefruit juice

Buspirone and Grapefruit Juice DRUG

Grapefruit juice will be given before and during buspirone administration to inhibit intestinal CYP3A4.

Buspirone; Buspirone plus grapefruit juice

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female
• Age 18-65 (inclusive, at time of informed consent)
• No tobacco use in the past three months.
• Underwent Roux-en-Y Gastric Bypass weight loss surgery 9-18 months prior to study OR has not had a weight loss surgery but matches the gastric bypass patients on age, gender, and BMI.
• Ability to read, write and understand English.
• Expresses the ability/willingness to consume grapefruit juice.

You may not qualify if:

• Taking a medication that has a clinically significant interaction with buspirone or grapefruit juice or an interaction that may alter the study data.
• Hypersensitivity to buspirone or any excipient contained within the dosage forms or grapefruit juice.
• Inability to tolerate repeated blood draws.
• Any history of bipolar disorder or a psychotic disorder.
• Current major depressive disorder or current suicidality.
• Alcohol or substance dependence in the past year.
• Currently pregnant or lactating or unwillingness to use medically accepted contraception during study.
• Taking a medication which significantly alters gastrointesinal transit time.
• Medical conditon which may increase participant risk with buspirone or grapefruit juice.
• Self reported history of viral hepatits or HIV.
• Positive urine drug screen unless documented prescription of a non-interacting medication.
• Renal impairment as evidenced by an estimated glomerular filtration rate (eGFR) of less than or equal to 60 ml/min/1.73 m2 or other abnormality on a renal panel that the medical provider feels puts the participant at risk.
• Hepatic insufficiency as defined by any hepatic enzyme greater than 3x the upper limit of normal or other hepatic laboratory abnormalities at the discretion of the medical provider.
• Any contraindication to bioelectrical impedance analysis (BIA) such as pregnancy, the presence of a pacemaker or other implanted mechanical device.

Sponsors & Collaborators

• North Dakota State University: lead
• Neuropsychiatric Research Institute, Fargo, North Dakota: collaborator

MeSH Terms

Interventions

Buspirone

Intervention Hierarchy (Ancestors)

Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 22, 2015
• First Posted: June 29, 2015
• Study Start: June 1, 2015
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: August 24, 2018

Record last verified: 2018-08