Thursday, 24 September 2015

QBW251 - what's it all about?

What is Cystic Fibrosis?

CF is a life-shortening inherited disease, affecting over 10,000 people in the UK.

You can't catch or develop CF. It's something you're born with. Most cases in the UK are now diagnosed soon after birth.

It causes thick, sticky mucus to build up in the lungs, digestive tract and other areas of the body.

The build up of mucus is caused by a defect in the CF gene chromosome, which results in a disruption of the trafficking chloride (salt) channels (called Cystic Fibrosis Trans-membrane conductance Regulator or CFTR) that are found on the cell surface (CFTR membrane).

In the normal healthy state, this allows the easy passage of substances to and from the cell surface. However in CF the disruption in the flow of these substances to and from the cell surface leads to the collection of sticky mucus.

The condition can cause life-threatening lung infections and serious digestive problems where reduced absorption of fats and proteins results in vitamin deficiency and malnutrition.

It is one of the most commonly inherited chronic lung diseases in children and young adults and is a life-threatening condition.

How will QBW251 help with CF?

QBW251 is a drug that may improve the activity of the defective chloride channel CFTR.

It is suggested that helping CFTR work better by adding QBW251 will result in improved salt transport at the cells surface. Therefore an improvement in the thick, sticky mucus, and an improvement in lung disease in CF patients.

Here is a video presentation for a drug called "Kalydeco", which does the same as QBW251, but for a different genotype.


What are the side effects of QBW251?

All drugs carry a risk of side effects. In Parts 1 and 2 of the study (healthy volunteers), there were no serious side effects seen and no side effects were seen that were related to volunteers discontinuing with the study.

The most common side effects of QBW251 observed in humans include: headache (15%, 15 patients in every 100), cough (6%, 6 patients in every 100), dizziness (5%, 5 patients in every 100), and flatulence (4%, 4 patients in every 100).

Apart from cough, these side effects were also commonly observed in humans treated with placebo. There were no abnormal clinical results (laboratory tests, vital signs and ECG) that were associated with exposure to QBW251 at any dose or exposure in either study part.

Changes in adrenal glands and kidneys have been seen in animals that have been given extremely high doses of QBW251 and there is a potential risk of diarrhoea. None of these adverse effects have been seen in the healthy volunteers who participated in parts 1 and 2 of this study.

Is QBW251 available on the market?

QBW251 is an “investigational drug”, which means that it is a medicine that is being tested and has not been approved by the regulatory agencies (health authorities) around the world.

QBW251 is currently not “on the market” in any country. The study drug is being used in this study for research purposes only, and will not be available to you to continue taking after this study has finished.

If I was to participate in the study, what will I have to do?

Visit Length of visit
(approx)
Description
Consent (Visit 0) 1.5 hours Read and sign consent forms.
Screening (Visit 1) 6 hours Study Doctor collects:
  • Basic information about you
  • Medical history
  • Details of current medical condition
  • Medication you are currently taking
  • Body measurements i.e. height, weight and vital signs (pulse, blood pressure, respiratory rate & body temperature)
  • Blood samples for CF genotyping, safety bloods (biochemistry, haematology) & HIV and Hepatitis blood screens
  • Alcohol, drugs & cotinine (to find if you smoke)
  • Pregnancy & follicle stimulation hormone test (for females)
  • Urine collection
  • ECG
  • Lung function
  • Pulse oximetry
  • Sputum collection
Day -1,
Baseline (Visit 2)
6 hours Baseline study evaluations will be conducted.

Repeat of some screening tests as followed:
  • Repeat assessment of the inclusion/exclusion criteria
  • Medical history & current condition
  • Physical examination
  • Pregnancy test (for females)
  • Body measurements
  • Vital signs
  • Blood sampling
  • ECG
  • Lung function
  • Sweat chloride assessment
  • Pulse oximetry
  • CF Quality of Life (CFQ-L) questionnaire
Day 1 (Visit 3) 9 hours On the evening before between 9pm & midnight, a salivary cortisol sample will be collected.

Blood samples for pharmacokinetics and blood, plasma and serum biomarkers will be taken before you receive your first dose of QBW251.

After this, a further 7 pharmacokinetic blood samples will be collected at 15 min, 30 min, 1 hour, 2 hours, 3 hours, 4 hours and 6 or 8 hours post treatment.

Repeat of some screening tests as followed:
  • Repeat body temperature 4 hours post treatment
  • Repeat vital signs and ECG tracing at 1, 2 and 6 or 8 hours post treatment
  • Biochemistry and haematology sampling along with repeat urinalysis at 4 & 6 or 8 hours post treatment.
The second dose of QBW251 will be administered 12 hours after the first dose.
Day 4 (Visit 4) 3 hours The next dose of QBW251 will be administered.

Repeat of some screening tests as followed:
  • Body weight/BMI
  • Vital signs
  • Body temperature
  • ECG
  • Urine collection
  • Blood sampling
  • Pulse oximetry
Day 7 (Visit 5) 5 hours On the evening before between 9pm & midnight, a salivary cortisol sample will be collected.

Repeat of some screening tests as followed:
  • Body weight/BMI
  • Vital signs
  • Body temperature
  • ECG
  • Urine collection
  • Blood sampling
  • Pulse oximetry
  • Lung function
  • Sweat chloride assessment
Day 14 (Visit 6) 5 hours On the evening before between 9pm & midnight, a salivary cortisol sample will be collected.

Repeat of some screening tests as followed:
  • CFQ-R questionnaire
  • Body weight/BMI
  • Vital signs
  • Body temperature
  • ECG
  • Urine collection
  • Blood sampling
  • Sweat chloride assessment
  • Pulse oximetry
Day 15,
Follow up (Visit 7)
1 hours Repeat of some screening tests as followed:
  • Lung function
  • Pulse oximetry
Day 28,
Follow up (Visit 8)
4 hours Repeat of some screening tests as followed:
  • Body weight/BMI
  • Vital signs
  • Body temperature
  • Urine collection
  • Blood sampling
  • Lung function
  • Sputum sampling
  • Sweat chloride assessment
  • Pulse oximetry
  • CFQ-R questionnaire
Day 42,
Follow up - End of Study (Visit 9)
3-4 hours On the evening before between 9pm & midnight, a salivary cortisol sample will be collected.

Repeat of some screening tests as followed:
  • Pregnancy test (for females)
  • Body weight/BMI
  • Vital signs
  • Body temperature
  • ECG
  • Blood sampling
  • Urine collection
  • Sputum sampling
  • Sweat chloride assessment
  • Pulse oximetry
  • CFQ-R questionnaire

You will need to:

  • Carry with you at all times a card (the same size as a credit card) which the study doctor will give you during the study. Cards like this are given to everyone who takes part in this kind of study; they include phone numbers to contact in any emergency.
  • Attend all of the study visits, and follow the instructions you are given. All of these visits will take place in your study hospital.
  • You may eat and drink normally whilst you are in the study, although we ask you to watch how much salt you eat and to eat some food just before you take each dose of your study treatment.
  • You will need to avoid being in direct sunlight, even if you cover your skin with clothes. If this will be difficult, your study doctor might suggest that you use tropical sub-blocking creams.
  • Tell your study doctor about any other medicines you are taking during the study. This is very important. This includes prescription drugs and over the counter medications (including creams and ointments, vitamins and supplements) that you take or use now, or intend to take — even ones you buy without a prescription. There are some drugs you are not allowed to take whilst you are on this study.
  • Tell your study doctor about any other conditions that you now or have suffered in the past.
  • Tell your study doctor if you have any unusual symptoms during the study.
  • Tell your study doctor if you want to stop being in the study at any time.
  • If you are a woman who could become pregnant:
    • You should not plan to become pregnant during the study, as we don’t yet know whether the study medicine is safe for an unborn baby.

      Women who are pregnant or nursing a child cannot take part in this study. You must confirm, to the best of your knowledge, that you are not now pregnant, and that you do not intend to become pregnant during the trial. The risks to an unborn human baby or a nursing child from the medications you are required to take in this study are not known.

      If you are female, to take part in the study you must be post-menopausal (no menses for at least 12 months) or be surgically sterile or use contraception methods listed below.

      The documented methods of surgical sterilization and contraception methods include:
      • having had a hysterectomy (removal of the uterus with or without the ovaries), or
      • bilateral oophorectomy (removal of both ovaries), or
      • A tubal ligation (having your tubes tied), or
      • Total abstinence (no sexual relations), when this is in line with your preferred and usual lifestyle. Periodic abstinence like calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal are not acceptable methods of contraception, or
      • Your sole partner is another woman, or
      • Your male partner has already been sterilized with the appropriate documentation. The sterilized male partner should be your sole partner, or
      • Using both of the following:
        • Placement of an intrauterine device (IUD) or intrauterine system (IUS), and
        • Use of an occlusive cap (diaphragm or cervical/vault cap) by you, or a condom by your male partner combined with a spermicidal foam/gel/film/cream/vaginal suppository.

Wednesday, 23 September 2015

QBW251 - Day -2: breathe in and relax

Day -2

Here is an account of what happened today:
6:00am Got up and showered.
6:30am

View from bedroom window


Ready for the big day
7:00am
Started my travel to hospital...
7:50am Arrived at the hospital.
8:40am By this time I had my BMI, temperature, blood pressure and ECG done.

Hardest part was to keep quiet during tests as talking would hinder the test and therefore would have to start again.  I wasn't allowed to do anything at all during the tests such as read, use mobile or listen to music for the same reason.
9:00am I was asked to do a urine sample mid-steam.  I asked where the nearest brook was.  I think the staff realised by this time I have a good sense of humour.
9:30am I did a breathing test 1/3, which took 7 minutes to complete.  I passed...I can breath!
9:45am Breathing test 2/3.  Guess what?  I passed again!  LOL
10:15am Breathing test 3/3.  I think I've convinced them now I can breathe.  No more breathing tests.
11:15am Lung function FEV1=2.15; FVC=4.65.
12:00pm Blood samples taken and all is done for today until Monday, 19 October 2015.
12:30pm
Home in time for lunch.

Tuesday, 22 September 2015

QBW251 - tick, initial, signature, date

Day -3

You may ask why I've put the day as -3 (minus three)?

Today was all about going through all the information with the Doctor about what the drug trial will involve.

I had to sign paperwork to show I understand what is to happen and that I consent to basically being a guinea pig.

The volunteers suite is stunning.  Whilst undergoing screening during this trial, I will have access to facilities such as a snooker room, cyber cafe, entertainment and relaxation room (where I can either play games on an X-box or watch DVDs, a small cafeteria and a self service refreshments section.  Plus my own relaxation garden.

I feel as though I'm going to be well looked after during this trial.

The people I saw were nice and very helpful in answering any questions asked.  Most of which were more because I was interested in what's going on rather than concerned.

Tomorrow, Day -2 I will have a screening assessment to see if I'm eligible to take part in this study.  Of course we all know already I am eligible.  However this is protocol.  This will involve taking basic information such as medical history,details of current medication and medical condition.  My BMI will be taken and vital signs i.e. pulse, blood pressure, respiratory rate and temperature.  I will undergo a full physical examination.

Blood samples will be taken for CF genotyping, safety bloods and other blood screens.

Other tests will include alcohol, drug and smoke tests.  Apparently I don't need to do a pregnancy test.  Though they will be taking the piss (a urine sample), doing an ECG and lung function.

Basically, by the end of the day, I will be poked, prodded, and pricked...nothing new here.  It will be like having an annual health assessment, but more thorough.

Early night to bed tonight.  I'm up at 6:30am so I can get ready to leave at 7am to be at the hospital for 8am.

More writings tomorrow to let you know how things go...goodnight from me and goodnight from him (now where did that quote come from?).

Monday, 21 September 2015

QBW251 - the trial study

On Wednesday, 16 September 2015 I had a port flush appointment at Wythenshawe Hospital.

During my appointment I was approached about taking part in a study to find out how the study drug, QBW251, works in the bodies of patients with CF.

I was given the opportunity to discuss this with family and friends before making up my mind.  However at the time of asking it wasn't made clear to me what drug I would be testing.

I requested more information on this to understand what was to happen.

Based on little information given at the time, I looked back over the last year or so to news items related to breakthrough medication for CF.

A story came to mind about a breakthrough in CF treatment for the lungs whereby the medication reversed or corrected the faulty gene (or something to that effect).

I suddenly had a feeling had I declined this opportunity, I would regret it.  So having spoken quickly to my dad and partner (by text), their encouragement confirmed this felt like the right thing to do.

Attempts were made to ring the hospital to confirm my interest in the study and it was a matter of time before I received the call I had been waiting for...the call that would be the beginning of a possible life changing experience.

Tomorrow (Tuesday, 22 September 2015), I will be attending my first appointment to go through processes and officially give my consent to be part of this study.

Come October, I will start trials of QBW251, a drug that may, when given to humans, improve the activity of the defective chloride channel CFTR, helping it to work better resulting in improved salt transport at the cells surface, lessen the thick, sticky mucus, and reduce lung disease in CF patients.

The only twist in this study is there is a chance I will be given a placebo...watch this space to see what happens over the next 2 months...