EP395 and drug combination (verapamil, midazolam, digoxin) pharmacokinetic study in healthy volunteers with COPD

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What is this study about?

The study involves healthy volunteers and focuses on understanding how medicines interact in people who may later have Chronic Obstructive Pulmonary Disease. The main goal is to find out whether one drug changes the amount of another drug that reaches the whole body.

In the first part, participants receive the test medicine called EP395 and then take the blood‑pressure medicine verapamil while continuing the same dose of EP395. This helps researchers see if verapamil changes the level of EP395 that stays in the body when the drug has reached a steady level, meaning the amount in the blood no longer rises or falls. In the second part, the same dose of EP395 is given together with two other medicines, the sleep‑inducing drug midazolam and the heart medication digoxin, to see whether EP395 alters how much of these drugs are present throughout the body.

Volunteers will visit the clinic several times to take the pills, have blood drawn, and undergo simple checks such as heart rhythm recordings and basic lab tests. Any unwanted symptoms or changes in vital signs are recorded. The study lasts for a short period, with each participant completing both sections under close medical supervision.

1 initial visit and baseline assessments

you will arrive at the study site after you have agreed to join the trial.

the study team will record your personal information, measure your vital signs, and perform basic safety laboratory tests.

a 12‑lead electrocardiogram (ecg) will be taken to check your heart rhythm.

2 part a – verapamil administration

you will start taking verapamil 240 mg film‑coated tablet by mouth each day.

the medication is taken once daily at the same time each day to reach a steady level in your body.

you will continue this dose for the period defined by the study protocol until steady state is achieved.

3 part a – ep395 administration and sampling

after verapamil has reached steady state, you will take a single dose of ep395 375 mg capsule by mouth.

blood samples will be collected at specified times after the dose to measure how much ep395 is in your system.

any adverse events you experience will be recorded by the study staff.

4 transition period

a short washout interval may be required before starting part b, during which no study medication is taken.

you will be monitored for safety and any lingering effects before beginning the next part of the trial.

5 part b – ep395 steady‑state dosing

you will begin taking ep395 375 mg capsule by mouth each day.

the dose is taken once daily at the same time each day until a steady level is reached in your body.

6 part b – midazolam and digoxin administration and sampling

once ep395 steady state is confirmed, you will take a single dose of midazolam 4 mg by mouth.

you will also take a single dose of digoxin 250 µg (0.25 mg) tablet by mouth.

blood samples will be collected at predefined times after each dose to evaluate how ep395 affects the levels of midazolam and digoxin.

any side effects or adverse events will be documented.

7 final assessments and study completion

at the end of the dosing periods, the study team will repeat vital signs, ecg, and safety laboratory tests.

all collected data will be reviewed, and you will be thanked for your participation.

you will receive a summary of the study results after the trial is fully analyzed.

Who Can Join the Study?

Must be willing and able to understand the study information and give written consent to take part.
Must be a healthy male or female aged between 18 and 55 years.
Must have a body mass index (BMI) of at least 19.0 and no more than 33.0 kg/m² (BMI is a simple calculation that compares weight to height).
Must be medically healthy with no significant medical history, normal physical exam, normal vital signs, a normal ECG (a test that records the heart’s electrical activity), and normal laboratory test results, as judged by the doctor.
Must be a non‑smoker, or if previously smoked, must have smoked less than 10 pack‑years (a pack‑year equals smoking one pack per day for one year) and must have stopped smoking (including e‑cigarettes) at least 6 months before screening.
Women who could become pregnant must have a negative pregnancy test at screening and on Day 1, must agree to use a highly effective form of birth control (failure rate less than 1 % per year) such as hormonal contraception plus a barrier method, an intrauterine device, sterilization, or agreed abstinence, and must not breast‑feed during the study and for 90 days after the last dose.
Women who cannot become pregnant are either post‑menopausal (no periods for at least one year) or have had surgical sterilization (such as tubal ligation, hysterectomy, or removal of both ovaries).
Men must use a condom with women who could become pregnant during treatment and for 90 days after the last dose, and must not donate sperm during that time.

Who Cannot Join the Study?

Any past serious illness that the doctor thinks could put you at risk, change the study results, or make it hard for you to take part.
Receiving a live vaccine (a vaccine that contains a weakened form of the germ) within the last 28 days, or any other vaccine within the last 14 days (COVID‑19 booster shots are allowed).
Testing positive for hepatitis B surface antigen, hepatitis C antibodies, or HIV (the viruses that cause hepatitis B, hepatitis C, or HIV infection) at the screening visit.
Testing positive for illegal drugs, nicotine (measured as cotinine), or alcohol at screening or before the first dose; a urine nicotine test of 200 ng/mL or higher also excludes you.
Having a history of alcohol abuse or drinking too much, as judged by the doctor.
Having a history of drug abuse, as judged by the doctor.
Having a history of using anabolic steroids (muscle‑building hormones), as judged by the doctor.
Drinking more than 5 cups of coffee (or an equivalent amount of other caffeinated drinks) each day, or being unable to avoid caffeine drinks, including energy drinks, during the trial.
Being a former smoker with more than 10 pack‑years (the equivalent of smoking one pack a day for 10 years), or having smoked (including e‑cigarettes or vapes) within 6 months before screening, or being unable to stay completely smoke‑free during the trial.
Using nicotine replacement products (such as patches, gum, or lozenges) within 2 weeks before screening and being unable to stay off them throughout the trial.
Being pregnant, currently breastfeeding, or planning to become pregnant at any time during the study.
Having any serious illness, surgery, or injury within 4 weeks before the first dose of the study drug.
Having a known allergy to macrolide antibiotics, to the study drug EP395, or to any of its inactive ingredients (dicalcium phosphate, croscarmellose sodium, magnesium stearate, microcrystalline cellulose).
Having a known allergy or a medical reason not to use verapamil (used in Part A) or digoxin or midazolam (used in Part B), as listed in the official drug information.
Having any significant allergy, as judged by the doctor.
Planning to take, or having taken, another investigational (experimental) drug within 5 half‑lives of that drug or within the last 3 months before the first dose, whichever is longer.
Being an employee of the sponsor company, or an employee or relative of the investigators.
Donating plasma within one month before screening, or donating blood (or losing a similar amount of blood) in the last three months before the first dose.
Being judged by the doctor as unlikely to follow the study’s rules, restrictions, and procedures.
Having any lung disease such as asthma or chronic obstructive pulmonary disease (COPD).
Having a serious gastrointestinal (stomach or intestine) condition that could affect how the drug is absorbed.
Having a current or past infection with tuberculosis (TB), or having lived with someone who had active TB at any time in the past 10 years.
Having a significant abnormal result on a 12‑lead ECG (heart electrical test) at screening or before the first dose, such as a prolonged QTcF interval (greater than 450 ms for men or 470 ms for women) or a PR interval longer than 210 ms.
Having abnormal kidney function at screening, shown by a serum creatinine level above the normal limit or an estimated glomerular filtration rate (eGFR) lower than 60 mL/min.
Having liver enzymes (AST or ALT) more than 1.5 times the upper limit of normal (ULN) at screening.
Taking prescription, over‑the‑counter, or herbal medicines within 28 days before the first dose, or being unable to stay off such medicines during the trial, except for hormone replacement therapy, contraception, or occasional use of paracetamol.

Where you can join this trial?

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Other Sites

Site Name	City	Country	Status
Cdk Chforqwp Tcibu Clzllbenaut Am	Uppsala	Sweden

Trial status

Country	Status	Recruitment Start
Sweden	Not recruiting	01.09.2023

Trial locations

Investigated Drugs:

EP395 is an experimental medicine that is being tested for the first time in humans. In the first part of the study, participants take EP395 alone and then together with another drug to see if the other drug changes how much EP395 gets into the bloodstream. In the second part of the study, participants take EP395 together with two other medicines to see if EP395 changes the amount of those medicines that appear in the blood.

Verapamil is a medication that relaxes blood vessels and is often used to treat high blood pressure and certain heart rhythm problems. In this trial it is given to healthy volunteers to find out whether it influences the amount of EP395 that reaches the bloodstream when both drugs are taken together.

Midazolam is a short‑acting sedative that is sometimes used before medical procedures to help people relax. In the study it is taken with EP395 so researchers can see if EP395 changes how much midazolam is absorbed and how long it stays in the body.

Digoxin is a medication that helps the heart beat more strongly and regularly, often used in people with heart failure or irregular heartbeats. In this trial it is taken together with EP395 to determine whether EP395 affects the amount of digoxin that reaches the bloodstream.

Investigated Diseases:

Chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) – COPD is a long‑term lung condition that makes breathing difficult. It often begins with a cough and mucus production, and shortness of breath worsens with activity. Over time the airways become narrowed and the lungs lose their stretch, leading to persistent breathlessness. Periodic worsening of symptoms, called exacerbations, can occur. The disease usually progresses slowly but can limit everyday tasks.

Trial ID:

2023-506345-34-00

Protocol code:

EP395-004

Trial Phase:

Human Pharmacology (Phase I) – Other

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EP395 and drug combination (verapamil, midazolam, digoxin) pharmacokinetic study in healthy volunteers with COPD

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?