Drug Interaction With Proton Pump Inhibitors for Nifedipine ER Tablets

NCT03100838 | Completed Phase 1 Results FDA Drug

• 1 other identifier: RIHSC 16-070D
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to measure the amount of study drug present in blood after being administered a generic version of nifedipine extended-release tablets, 60 mg (Valeant Pharmaceuticals, LLC) and brand-name version PROCARDIA XL extended-release tablets, 60 mg (Pfizer Inc.) individually and in presence of stomach acid reducing drug (antacid), omeprazole/sodium bicarbonate capsules, 40 mg/1100 mg (generic) on separate occasions, on an empty stomach. This study also involves administrations of an FDA-cleared capsule, SmartPill™, which will measure stomach acid, prior to each study arm.

Conditions

Healthy Volunteers

Keywords

Proton Pump Inhibitor; Bioequivalence; Drug-Drug Interaction; Modified Release; Nifedipine

Outcome Measures

Primary Outcomes (4)

• Maximum Plasma Concentration (Cmax)

  Measurement of plasma nifedipine prior to dosing and at times 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 20, 24, 36 and 48 hr after nifedipine administration.

  48 hours

• Time at Maximum Plasma Concentration (Tmax)

  Measurement of plasma nifedipine prior to dosing and at times 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 20, 24, 36 and 48 hr after nifedipine administration.

  48 hours

• Area Under the Concentration (AUC 0-t)

  Time curve from time zero to last measurable concentration. Measurement of plasma nifedipine prior to dosing and at times 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 20, 24, 36 and 48 hr after nifedipine administration.

  48 hours

• Half-life

  The apparent terminal exponential half-life. Measurement of plasma nifedipine prior to dosing and at times 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 20, 24, 36 and 48 hr after nifedipine administration.

  48 hours

Secondary Outcomes (1)

• Adverse Events

  66 days

Study Arms (4)

Nifedipine (Generic)

EXPERIMENTAL

1 x 60 mg Nifedipine extended-release tablet

Drug: Nifedipine 60 MG Extended Release Oral Tablet; Device: SmartPill (TM)

Nifedipine (Brand)

ACTIVE COMPARATOR

1 x 60 mg PROCARDIA XL (nifedipine) extended-release tablet

Drug: Nifedipine 60 MG Extended Release Oral Tablet; Device: SmartPill (TM)

Nifedipine (Generic) + PPI

ACTIVE COMPARATOR

1 x 40 mg/1100 mg omeprazole/sodium bicarbonate capsule daily over a period of 7 days + 1 x 60 mg Nifedipine extended-release tablet on day 7

Drug: Nifedipine 60 MG Extended Release Oral Tablet; Drug: omeprazole/sodium bicarbonate; Device: SmartPill (TM)

Nifedipine (brand) + PPI

ACTIVE COMPARATOR

1 x 40 mg/1100 mg omeprazole/sodium bicarbonate capsule daily over a period of 7 days + 1 x 60 mg PROCARDIA XL (nifedipine) extended-release tablet on day 7

Drug: Nifedipine 60 MG Extended Release Oral Tablet; Drug: omeprazole/sodium bicarbonate; Device: SmartPill (TM)

Interventions

Nifedipine 60 MG Extended Release Oral Tablet DRUG

Reference Drug (Brand)

Also known as: Procardia XL

Nifedipine (Brand); Nifedipine (brand) + PPI

omeprazole/sodium bicarbonate DRUG

Proton Pump Inhibitor/Antacid for drug-drug interaction

Nifedipine (Generic) + PPI; Nifedipine (brand) + PPI

SmartPill (TM) DEVICE

Gastric pH measurement using SmartPill (TM) Technology

Nifedipine (Brand); Nifedipine (Generic); Nifedipine (Generic) + PPI; Nifedipine (brand) + PPI

Eligibility Criteria

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

You may qualify if:

• Healthy, males and non-pregnant female volunteers, 18 to 55 years of age, inclusive.
• Smoking status: Only non-tobacco/nicotine users (for at least 6 months prior to the clinical study) will be eligible to participate in this study.
• BMI that is within 18.5-35.0 kg/m², inclusive.
• Healthy, according to the medical history, ECG, vital signs, laboratory results and physical examination as determined by the PI/Sub-Investigator.
• Ability to comprehend and be informed of the nature of the study, as assessed by BPSI staff. Capable of giving written informed consent prior to receiving any study procedure. Must be able to communicate effectively with clinic staff.
• Ability to fast for at least 14 hours.
• Availability to volunteer for the entire study duration and willing to adhere to all protocol requirements.
• Female subjects must fulfill at least one of the following:
• Be surgically sterile for a minimum of 6 months;
• Post-menopausal for a minimum of 1 year;
• Agree to avoid pregnancy and use medically acceptable method of contraception from at least 30 days prior to the study until 30 days after the study has ended (last study procedure).
• Medically acceptable methods of contraception include non-hormonal contraceptives, intrauterine device, or double barrier method (condom with foam or vaginal spermicidal suppository, diaphragm with spermicide). Complete abstinence alone can be used as a method of contraception.

You may not qualify if:

• Known history or presence of any clinically significant hepatic, renal/genitourinary, gastrointestinal (e.g., gastrointestinal obstruction, gastrointestinal ulcers), cardiovascular (e.g., severe obstructive coronary artery disease, myocardial infarction, angina, heart failure), cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological or hematological disease or condition unless determined as not clinically significant by the PI/Sub-Investigator.
• Clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel disease), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting, swallowing disorder), or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug experienced within 7 days prior to first dosing, as determined by the PI/Sub-Investigator.
• QTc interval \> 430 milliseconds for males and \> 450 milliseconds for females, unless deemed otherwise by the PI/Sub-Investigator.
• Abnormal clinical laboratory values, unless values are deemed by the PI/Sub-Investigator as "Not Clinically Significant".
• Hemoglobin values less than 11.5 g/dl.
• Abnormal vital signs (blood pressure \[BP\], heart rate \[HR\], respiratory rate \[RR\] and temperature) measurements, unless deemed otherwise by the PI/Sub-Investigator.
• Presence of any clinically significant illness within 30 days prior to first dosing, as determined by the PI/Sub-Investigator.
• Presence of any significant physical or organ abnormality as determined by the PI/Sub-Investigator.
• Individuals who have implanted or portable electro-mechanical medical device such as a cardiac pacemaker, defibrillator or infusion pump.
• A positive test result for any of the following: HIV, Hepatitis B surface antigen, Hepatitis C, drugs of abuse (marijuana, amphetamines, barbiturates, cocaine, opiates, phencyclidine and benzodiazepines), alcohol test and cotinine. Positive pregnancy test for female subjects.
• Known history or presence of:
• Alcohol abuse or dependence within one year prior to first study period;
• Drug abuse or dependence;
• Hypersensitivity or idiosyncratic reaction to nifedipine, omeprazole/sodium bicarbonate, its excipients, and/or related substances;
• Hypotension;

Sponsors & Collaborators

• Food and Drug Administration (FDA): lead
• BioPharma Services Inc.: collaborator

Study Sites (1)

BioPharma Services Inc.

Columbia, Missouri, 65201, United States

Location

MeSH Terms

Interventions

Nifedipine; omeprazole, sodium bicarbonate drug combination

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Minori Kinjo
• Organization: USFDA

minori.kinjo@fda.hhs.gov

240-40269118

Study Officials

• Kathleen Doisy

  BioPharma Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Model Details: A single-dose, randomized, open-label, drug-drug interaction (DDI), 4-way crossover, four-treatment, four-sequence, bioequivalence study

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: April 4, 2017
• Study Start: March 20, 2017
• Primary Completion: December 23, 2017
• Study Completion: April 6, 2018
• Last Updated: August 16, 2019
• Results First Posted: July 22, 2019

Record last verified: 2019-08

Locations

US (1)