Study Assessing the Safety, Tolerability, Pharmacokinetics, Food Effect, and Drug-Drug Interactions of PTI-801 in Healthy Volunteers, and Safety, Tolerability, and Pharmacokinetics of PTI-801 in Subjects With Cystic Fibrosis



Status:Recruiting
Conditions:Healthy Studies, Pulmonary
Therapuetic Areas:Pulmonary / Respiratory Diseases, Other
Healthy:No
Age Range:18 - Any
Updated:1/23/2019
Start Date:April 10, 2017
End Date:June 2019
Contact:Proteostasis Clinical Trials
Email:pticlinicaltrials@proteostasis.com
Phone:1-866-223-3262

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A Multi-Center, Randomized, Placebo-Controlled, Phase 1, Two-Part Study Designed to Assess the Safety, Tolerability, Pharmacokinetics, Food Effect, and Drug-Drug Interactions of PTI-801 in Healthy Volunteers, and Safety, Tolerability, and Pharmacokinetics of PTI-801 in Subjects With Cystic Fibrosis

This trial will consist of two parts: Part 1 and Part 2. Part 1 will enroll adult healthy
volunteers (HV) into four treatment groups. The first group will enroll HV into a single
ascending dose (SAD) treatment group consisting of three cohorts. The second group will
enroll HV into a multiple ascending dose (MAD) treatment group consisting of three cohorts.
The third group will enroll HV into a food effect (FE) treatment group consisting of one
cohort. The fourth group will enroll HV into a drug-drug interactions (DDI) treatment group
consisting of one cohort. Approximately 76 subjects will be enrolled in Part 1.

Part 2 Cohorts 1 through 3 will enroll adult subjects with cystic fibrosis (CF) currently on
stable ivacaftor/lumacaftor background therapy for a minimum of three months. Part 2 Cohorts
4 and Cohort 5 will enroll adult subjects with CF not currently receiving cystic fibrosis
conductance regulator (CFTR) modulator therapy within 30 days prior to Day 1. Part 2 Cohort 6
will enroll adult subjects with cystic fibrosis on stable tezacaftor/ivacaftor background
therapy. Approximately 104 subjects will be enrolled in Part 2.

PART 1 The SAD treatment group is comprised of three cohorts where HV will be randomized to
either PTI-801 or placebo. The MAD treatment group is comprised of three cohorts where
subjects will be randomized to receive either PTI-801 or placebo once daily (QD) for a total
of 7 days. HV will participate in a FE treatment group ,the FE treatment group is comprised
of one cohort where subjects will be randomized to receive an initial single dose of PTI-801
either after an overnight fast of at least 10 hours (fasted group) or after an overnight fast
of at least 10 hours followed by the consumption of a high fat high and high calorie meal
(fed group). A set of HV will participate in a DDI treatment group. The DDI treatment group
is comprised of one cohort where subjects will receive a 3-drug cocktail consisting of
caffeine, bupropion, and midazolam on Day 1. On Day 4, subjects will be randomized to receive
either PTI-801 or placebo QD for a total of 12 days. On Day 17, subjects will receive the
3-drug cocktail in combination with PTI-801 or placebo.

PART 2 Part 2 is comprised of a MAD treatment group with three cohorts, a co-administration
group with two cohorts and a treatment group with one cohort.

Following the conclusion of the complementary HV MAD Cohort in Part 1, a set of adult
subjects diagnosed with CF currently on a stable ivacaftor/lumacaftor background therapy for
a minimum of three months will participate in the Part 2 complementary CF MAD cohort.
Subjects will be randomized to receive either PTI-801 or placebo QD for a total of 14 days.

Following the conclusion of CF MAD Cohort 1 in Part 2, a set of adult subjects diagnosed with
CF not currently receiving or have received background CFTR modulator therapy for a minimum
of 30 days prior to Day 1 will participate in the Part 2 CF PTI-801 and PTI-808
co-administration cohort. Subjects will be randomized to receive either PTI-801
co-administered with PTI-808 or placebos QD for a total of 14 days.

Following the conclusion of the CF MAD Cohort 1 in Part 2, a set of adult subjects diagnosed
with CF currently on a stable tezacaftor/ivacaftor background therapy for a minimum of one
month will participate in the Part 2 complementary CF cohort. Subjects will be randomized to
receive either PTI-801 or placebo QD for a total of 14 days.

Part 1 Inclusion Criteria:

- Adults age 18 to 55 years old, inclusive, at the time of informed consent.

- Body mass index (BMI) ≥18 to <30 kg/m2.

- Subject must be a nonsmoker and a nontobacco user for a minimum of 30 days prior to
screening and for the duration of the study.

Part 1 Exclusion Criteria:

- History or current evidence of any clinically significant cardiac,
endocrinologic,hematologic, hepatobiliary, immunologic, metabolic, urologic,
pulmonary, neurologic,dermatologic, psychiatric, renal, or other major disease, as
determined by the investigator.

- Presence of prolonged QT/ Corrected QT Interval (QTc) interval with Fridericia's
correction formula (QTcF) >450 msec at screening.

- Abnormal liver function as defined by aspartate aminotransferase (AST), alanine
aminotransferase (ALT) or bilirubin > upper limit of the normal range.

- Abnormal renal function at screening defined as: Creatinine clearance <80 mL/min using
the Cockcroft-Gault equation.

- Participation in another clinical trial or treatment with an investigational agent
within 30 days or 5 half-lives, whichever is longer, prior to Study Day 1.

- History of cancer within the past 5 years (excluding nonmelanoma skin cancer).

- History or current evidence of alcohol or drug abuse or dependence within 12 months of
screening as determined by the investigator.

- Positive urine screen for prohibited drugs (cocaine, cannabinoids, nicotine [urine
cotinine is the detection mechanism for nicotine], opiates, barbiturates,
amphetamines, and benzodiazepines) or positive alcohol test at screening.

- Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface
antigen (HBsAg), or hepatitis C virus antibody (HCVAb).

- Has donated blood within 3 months of screening or plans to donate blood within 3
months of study completion.

Part 1 HV DDI Cohort Additional Exclusion Criteria:

- Concomitant use of known strong or moderate inhibitors or inducers of CYP1A2, CYP2B6,
and CYP3A4 within 14 days or 5 half-lives (whichever is longer) prior to Day 1 and
through the last PK sampling point on Day 20

- Use of grapefruit- or Seville orange-containing products within 48 hours prior to Day
1 and through the last PK sampling point on Day 20

- Use of alcohol- or caffeine-containing products within 48 hours prior to Day 1 and
through the last PK sampling point on Day 20

Part 2 Inclusion Criteria:

- Confirmed diagnosis of CF with the F508del/F508del genotype on record, along with
clinical findings consistent with CF such as chronic sinopulmonary disease or
gastrointestinal/nutritional abnormalities

- Forced expiratory volume in 1 second (FEV1) 40-90% predicted, inclusive

- Non-smoker and non-tobacco user for a minimum of 30 days prior to screening

Part 2 Cohorts 1-3 Additional Inclusion Criterion:

- Stable on ivacaftor/lumacaftor dosing for both label indication and per label dosing
for a minimum of 3 months at the time of dosing

Part 2 Cohort 6 Additional Inclusion Criterion:

- Stable on tezacaftor/ivacaftor dosing for both label indication and per label dosing
for a minimum of 1 month at the time dosing

Part 2 Exclusion Criteria:

- Participation in another clinical trial or treatment with an investigational agent
within 28 days or 5 half-lives, whichever is longer, prior to Study Day 1

- History of cancer within the past 5 years (excluding cervical cancer in situ with
curative therapy for at least one year prior to screening and non-melanoma skin
cancer)

- History of organ transplantation

- Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically
significant infection or illness (as determined by the investigator) requiring an
increase or addition of medication, such as antibiotics or corticosteroids, within 14
days of Day 1

- Initiation of any new chronic therapy (e.g., ibuprofen, hypertonic saline,
azithromycin, Pulmozyme®, Cayston®, TOBI®)) or any change in chronic therapy
(excluding pancreatic enzyme replacement therapy) within 28 days prior to Day 1

- History or current evidence of alcohol or drug abuse or dependence within 12 months of
screening as determined by the investigator

- Pregnant or nursing women

Part 2 Cohort's 4 and 5 Additional Exclusion Criterion:

- Currently taking or has taken a CFTR modulator within 30 days prior to initial dose of
study drugs
We found this trial at
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Chicago, Illinois 60611
Phone: 312-695-0415
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1 Perkins Square
Akron, Ohio 44308
(330) 543-1000
Phone: 330-543-3089
Akron Children's Hospital From humble beginnings as a day nursery in 1890, Akron Children
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1720 2nd Ave S
Birmingham, Alabama 35233
(205) 934-4011 
Phone: 205-638-5970
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185 Cambridge Street
Boston, Massachusetts 02114
617-724-5200
Phone: 617-726-3719
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700 Childrens Drive
Columbus, Ohio 43205
(616) 722-2000
Phone: 614-722-4756
Nationwide Children's Hospital At Nationwide Children’s, we are creating the future of pediatric health care....
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101 Jessup Hall
Iowa City, Iowa 52242
(319) 335-3500
Phone: 319-384-7546
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4401 Penn Avenue
Pittsburgh, Pennsylvania 15224
412-692-5325
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22 Bramhall St
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201 Presidents Circle
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40 Sunshine Cottage Road
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Altamonte Springs, Florida 32701
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Anchorage, Alaska 99508
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1500 E Medical Center Dr
Ann Arbor, Michigan 48109
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Boise, Idaho 83712
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300 Longwood Ave
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171 Ashley Avenue
Charleston, South Carolina 29425
843-792-1414
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1400 Jackson St
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300 Pasteur Dr
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