My Participation in a Phase1b, Open Label Study of Siena Biotech’s Drug SEN0014196 (Selisistat)

n January, 2012 I was asked to participate in this study being conducted by the Clinical Research Unit (CRU) of the Wake Forest University Baptist Medical Center in Winston-Salem, NC. This was to be a short, but intense study evaluating the safety of a promising new drug for the treatment of Huntington’s Disease.

Selisistat is a SIRT1 Inhibitor (sirtuin deacetylase) that is thought to selectively reduce levels of the mutant htt protein, acting as a true disease modifier. This study would look at how the body is reacting to the drug (pharmacokinetics, or PK) and what the drug is doing to the body (pharmacodynamics, or PD). Both would be measured with multiple blood tests over a 14 day dosing period. To insure my safety, vital signs and heart function (ECG) would be closely monitored. I would be randomly assigned to either a fasting or fed group for dosage timing analysis.

It took me about 10 seconds to decide to volunteer.

I had an initial screening visit on April 30th to see if I would qualify. I had the most important inclusionary item, a positive test result for HD (CAG 40). There are a great number of exclusionary items that luckily did not apply to me. I do have a harmless heart condition called a right branch bundle block. That sounds terrible, but it’s only a timing difference between electrical impulses that fire the two sides of my heart. I also once had a false positive test for Hepatitis C as a blood donor. The study coordinator confirmed that these two issues would not disqualify me.

For a number of years my blood pressure has experienced wide swings due to “White Coat Syndrome”. I have used a home monitor for about 5 years, and it is almost always normal when I take it anywhere outside a medical environment. Well, during my screening visit it decided to throw a childish temper tantrum and read about 200 over 100. That even rattled the coordinator, who is familiar with my blood pressure issue from the COHORT study. I promised to do daily readings for the next 7 days before the study start date on May 8th.

My home BP readings were all in the normal range and the standard blood lab work from the screening visit was perfect. Those fully qualified me for the study and I arrived at the CRU at 6:30 AM on May 8th ready to rock and roll. The first step was a complete physical, neurological and psychological exam by the study doctor, including an ECG. The purpose was to make sure I was still healthy enough for the study and to set baselines for any changes due to the drug. None were expected due to the short duration, but the exams would be repeated on the last day of the drug dosage period to confirm. My BP even behaved that morning.

The next step was for the great study computer in the sky to randomly assign me to either a “Fed” or “Fasted” group to determine whether I would take the drug on a full or empty stomach for the duration of the study. I got lucky and was assigned to the Fed group. That meant I would have a controlled breakfast prepared by the CRU staff right away. I had been fasting since midnight, so that was welcome news. If I had been assigned to the Fasting group I would have taken the drug right away and have had to fast for another 4 hours.

While my breakfast was being prepared, my nurse took baseline blood samples for PK and PD. A needle was left in my arm with a small valve device for frequent blood to be drawn during the day. It was securely taped to my arm and was comfortable for the next 9 hours.

The study coordinator witnessed my breakfast and then gave me the first dose of the drug. I’m not sure what I expected, but I was surprised that the pill was just a little larger than an aspirin. I couldn’t help but marvel that years of research and a whole lot of money were now reduced to one tiny disc. In the days to come I would notice a slight feeling of lightheadedness and weakness right after taking the drug. It would last for 2 or 3 hours, but was not at all troublesome. I didn’t notice it the first day.

Following the initial dosage, blood was drawn after 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours. Separate samples were drawn for both PK and PD testing. I wouldn’t know a PK result from a list of curling scores, but I tried to nod intelligently when the nurse made some comment about them. Another ECG was done 3 hours after the first drug dose.

All of these events were timed with a timer down to the second. It was quite impressive. Late in the day I was killing time before the last draw wandering around the clinic. I noticed an odd looking device with a small computer screen and asked my nurse what it was. She laughed and said “It’s a defibrillator”. I’m glad I didn’t need that one, but it was good to know it was there.

After the final blood draw I was released. I had to fast again after midnight and returned to the clinic at 8:30 AM the next morning. A urine sample was taken and two more blood samples for PK and PD were drawn exactly 24 hours after the initial drug dose at 8:42 AM. I was given the entire drug supply and then released. It had been a long day and a half.

On May 14th I returned to the clinic for a brief Day 7 visit. A urine sample and a standard blood sample (not PK or PD) were taken along with my vital signs. I reported the feeling of lightheadedness to the study coordinator. On Day 8 the feeling was much less than it had been, perhaps due to my body getting used to daily doses of the drug.

On Monday, May 21st I arrived at the CRU at 7:00 AM for the final two days of the study. Since I was already assigned to the Fed group, I ate a controlled breakfast and took the final drug dose. The same schedule would be followed for blood draws and an ECG as on Day 1. During the day the study doctor repeated the same physical, neurological and psychological exams that had been done on Day 1. Unfortunately, that valve or catheter device that worked well during the May 8th visit malfunctioned after the first blood draw. All the rest had to be done with separate needle sticks. I was starting to run out of good veins by the end of the day. Luckily needles don’t bother me. After the final blood draw I was released for the day. I had to fast again after midnight and returned to the clinic at 8:30 AM the next morning. Two more blood samples for PK and PD were drawn exactly 24 hours after the final drug dose.

Two weeks after the final dose, I will return for a follow-up visit. Urine and blood samples (for PD only) will be taken along with my vital signs. Any lingering adverse effects of the study will be reported.

I was extremely impressed with the conduct of the study. Dr. Francis Walker, the study doctor and Christine O’Neill, the study coordinator, were knowledgeable and professional at all times. Dr. Walker is also the Principal Investigator for the entire study. The nurses who assisted them were also great. This was an incredibly complicated study and it was executed flawlessly. I told Christine I would be happy to come back (hopefully soon) for a Phase 2 trial.