PRA-183731

Liver disease

Study of a new compound that is being developed for the treatment of the liver disease non-alcoholic steatohepatitis (NASH)

Particulars

  • we are looking for healthy males and females between 18 and 45 years old.
  • Both non-smokers and smokers or social smokers are allowed to participate in this study; however, during your stay in the research facility, smoking is not allowed.
  • You can only participate in this study if you are using sufficient contraception or when you (or your partner) have been surgically sterilized. Women can also participate if you are postmenopausal for at least one year.
  • To determine if you are suitable to participate in this study, you will undergo a pre-screening. The pre-screening consists of a medical screening and right before the start of the study a ‘tyramine challenge’. During this ‘challenge’ you will stay maximally 11 days (10 nights) in our research facility during which you will receive tyramine maximally 10 days in ascending doses to investigate the effect on your blood pressure. Tyramine is a natural product that is present in certain foods and beverages like old cheese and red wine for example. Depending on the results, it is possible that you will be discharged earlier, but also that you cannot continue with the study after this period.
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Compensation

You will receive a gross compensation of €4,836.- for participation in one of the groups of part 1 or 2 of this study (group A1 to A8).
For participation in one of the groups of part 3 (groups B1 to B4) of the study, you will receive a gross compensation of €4,545.-.
When you cannot continue with the study after the ‘tyramine challenge’, you will receive a gross compensation of €1,776.- for your participation.

Travelling expenses will be reimbursed based on the distance traveled (€0.19 net per kilometer) with a minimum of €12.- and a maximum of €160.- (840 kilometers) per return, regardless of the mode of transportation.

Period of stay and research

The study consists of 3 parts.

Part 1 and 2 (groups A1 to A8) of the study consist of 5 periods during which you will stay the first four periods each for 2 days (1 night) in our research facility in Groningen. During the fifth period you will stay maximally 16 days (15 nights) in our research facility.
Part 3 (groups B1 to B4) of the study consists of 1 period during which you will stay maximally 20 days (19 nights) in our research facility in Groningen.

During period 5 of parts 1 and 2 (groups A1 to A8) and at the end of part 3 (groups B1 to B4) , there will be another ‘tyramine challenge’. Again, depending on the results, it is possible that you will be discharged earlier. Finally, there will be a follow-up visit after the study.

Please note: Including the pre-screening part, the duration of parts 1 and 2 can be maximally 35 days (29 nights) and for part 2 maximally 31 days (30 nights). You have to be available for all dates for the group of choice to be able to participate in this study. The actual dates will be published on our website. These are the currently planned dates; however, these may be subject to change.

More info

Type of study

NASH is abnormal fat build-up in the liver that is not caused by excessive alcohol consumption. In addition, there is liver inflammation which results to liver damage. The purpose of the study is to investigate the effect of the study medication on the systolic blood pressure, when administered together with tyramine. The effect of the study medication on the systolic blood pressure will be compared with placebo and phenelzine. In addition, it will be investigated to what extent the study medication is safe and tolerated. It will also be investigated how quickly and to what extent the study medication is absorbed and eliminated from the body. The study drug is not registered as a drug but has been given to humans before. The study will only take place after it has been approved by the Independent Ethics Committee

Setup and duration of the study

The actual study will consist of 3 parts. To determine if you are suitable to participate in this study, you will undergo a pre-screening. The pre-screening consists of a medical screening and right before the start of the study a ‘tyramine challenge’. During this ‘challenge’ you will stay maximally 11 days (10 nights) in our research facility during which you will receive tyramine maximally 10 days in ascending doses to investigate the effect on your blood pressure. Tyramine is a natural product that is present in certain foods and beverages like old cheese and red wine for example. Depending on the results, it is possible that you will be discharged earlier, but it is also possible that you cannot continue with the study after this period if your blood pressure does not rise above the predefined levels.

Part 1 and 2 of the study consist of 5 periods during which you will stay the first four periods each for 2 days (1 night) in our research facility in Groningen. During the fifth period you will stay maximally 16 days (15 nights) in our research facility. Part 3 of the study consists of 1 period during which you will stay maximally 21 days (20 nights) in our research facility in Groningen. During period 5 of parts 1 and 2 and at the end of part 3, there will be another ‘tyramine challenge’. Again, pending on the results, it is possible that you will be discharged earlier. Finally, there will be a follow-up visit after the study.

Please note: Including the pre-screening part, the duration of parts 1 and 2 can be maximally 35 days (29 nights) and for part 3 maximally 32 days (31 nights).

In parts 1 and 2 you will receive the study drug or placebo repeatedly over maximally 39 days in the form of a tablet. In addition, you will receive tyramine repeatedly during period 1 (maximally 10 days) and 5 (maximally 11 days) in the form of a capsule. In part 3 you will receive phenelzine repeatedly over maximally 19 days in the form of a tablet. In addition, you will receive tyramine maximally 10 days at the start and maximally 12 days at the end of the study in the form of a capsule. Depending on the results of the tyramine challenge on your blood pressure, it is possible that you will be discharged earlier in parts 1 and 2 during periods 1 and 5. Also in part 3 it is possible that you will be discharged earlier. Blood samples will be taken, and urine will be collected regularly during the study.

Please note: You have to be available for all dates for the group of choice to be able to participate in this study.

Risks and medical supervision

The study medication is able to block a specific protein that has an important role in various forms of inflammation. By blocking this protein, the inflammation and build-up of fat in the liver may be reduced. The study medication has been administered in a total of 108 volunteers in 2 previous clinical studies. Overall, the study medication was well tolerated in both studies. The most reported side effects were headache and gastro-intestinal disorders. These were of mild severity. The study medication may also have side effects that are still unknown. The most reported side effects from phenelzine were dizziness, headache and obstipation. In addition, tyramine can lead to high blood pressure and headache. You will be under strict medical supervision during the study. Before the study and at the end of the study you will undergo an extensive medical screening.

Conditions for participation

You are a healthy male or female between 18 and 45 years old. You can only take part in the study if you do not smoke or are a mild smoker. You can only participate in this study if you are using sufficient contraception or when you (or your partner) have been surgically sterilized. Women can also participate if you are postmenopausal for at least one year. The study will be executed under standardized conditions. Use of your own medication, alcohol, regular coffee and tea, cola, power drinks, chocolate (including products made of chocolate), grapefruit (juice) and tobacco products during the study is not allowed. Also before the study there will be restrictions for these products. Use of decaffeinated coffee and (herbal) teas without caffeine is allowed. Before you are allowed to take part in the study, you will be medically screened; this screening will take place within approximately three weeks before the start of the study.

Sign up for one of the following study groups

Group A3 Males

3× 2 days, 13 days en 16 days stay

  • 12 Dec 2019 up to and including 24 Dec 2019
  • 29 Dec 2019 up to and including 30 Dec 2019
  • 5 Jan 2020 up to and including 6 Jan 2020
  • 12 Jan 2020 up to and including 13 Jan 2020
  • 17 Jan 2020 up to and including 1 Feb 2020
€ 4.836,- Select

Groep B3 Females

32 days stay

  • 4 Jan 2020 up to and including 4 Feb 2020
€ 4.545,- Select
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Group B1

Full

32 days stay

  • 15 Aug 2019 up to and including 15 Sep 2019
€ 4.545,- Select

Group B2

Full

32 days stay

  • 19 Sep 2019 up to and including 20 Oct 2019
€ 4.545,- Select

Group A1

Full

3× 2 days, 12 days en 16 days stay

  • 25 Oct 2019 up to and including 5 Nov 2019
  • 11 Nov 2019 up to and including 12 Nov 2019
  • 18 Nov 2019 up to and including 19 Nov 2019
  • 25 Nov 2019 up to and including 26 Nov 2019
  • 30 Nov 2019 up to and including 15 Dec 2019
€ 4.836,- Select

Group A2

Full

3× 2 days, 13 days en 16 days stay

  • 28 Nov 2019 up to and including 10 Dec 2019
  • 15 Dec 2019 up to and including 16 Dec 2019
  • 22 Dec 2019 up to and including 23 Dec 2019
  • 29 Dec 2019 up to and including 30 Dec 2019
  • 3 Jan 2020 up to and including 18 Jan 2020
€ 4.836,- Select