Clinical Study to Investigate the Urinary Excretion of N-nitrosodimethylamine (NDMA) After Ranitidine Administration

Summary

Ranitidine is an over-the-counter and prescription drug, which decreases the amount of acid secreted by the stomach. Some ranitidine medicines contain an impurity called N-nitrosodimethylamine (NDMA) at low levels. NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables.

The US Food and Drug Administration (FDA) has found levels of NDMA in some ranitidine products similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats. The ranitidine that will be used in this study has been tested twice (months apart) and shown to have stable NDMA levels well below the acceptable daily limit. Of note, the risk of NDMA with ranitidine is only relevant with prolonged chronic administration as at the acceptable limit, there is approximately a 1 in 100,000 chance of cancer after 70 years of exposure to that level.

FDA has also conducted tests that simulate the potential formation of NDMA from ranitidine after it has been exposed to acid in the stomach with a normal diet. Results of these tests indicate that NDMA is not formed in typical stomach conditions. Similarly, if ranitidine is exposed to a simulated small intestinal fluid, NDMA is not formed. Other laboratory experiments suggest a combination of nitrites, such as found in processed meats, and an acidic environment may increase NDMA formation, however the levels of nitrites tested were very high. Separately, a previous study in 10 healthy volunteers showed that volunteers who received ranitidine had an increase in urinary NDMA excreted over 24 h. The level of increase was greater than would be expected from laboratory testing.

This clinical study is being performed to determine if and how much NDMA is produced from ranitidine in the human body and whether nitrite-containing foods may increase formation of NDMA. The study will use a prescription dose of ranitidine (300 mg) to test whether there is increased urinary NDMA excretion levels over 24-hours after ranitidine administration in comparison to placebo when participants are administered low nitrite/NDMA meals and when subjects are administered high nitrite/NDMA meals. On 4 different days, each participant will receive ranitidine or placebo with high nitrite/NDMA meals and ranitidine or placebo with low nitrite/NDMA meals.

Conditions

• Ranitidine Adverse Reaction
• Pharmacokinetics
• Food-drug Interaction

Interventions

DRUG

Ranitidine

Ranitidine 300 mg

DRUG

Placebo

Oral placebo tablet

OTHER

Low nitrite/NDMA meals

Meals containing low levels of nitrites and NDMA

OTHER

High nitrite/NDMA meals

Meals containing higher levels of nitrites and NDMA

Sponsors & Collaborators

• Spaulding Clinical Research LLC

  collaborator OTHER

• Food and Drug Administration (FDA)

  lead FED

Principal Investigators

• Colleen Nalepinski, MPAS, PA-C · Spaulding Clinical Research LLC

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-06-08

Primary Completion

2020-07-01

Completion

2020-07-01

FDA Drug

Yes

Countries

• United States

Study Locations