Study Designed to Assess the Safety, Tolerability and PK of PTI-808 in Healthy Volunteers and in Adults With Cystic Fibrosis
Condition: Healthy Volunteer - Complete; Cystic Fibrosis - Complete
MeSH terms: Cystic Fibrosis; Fibrosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD),
      multiple ascending dose (MAD), and Food Effect (FE) treatment groups.

      The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy
      adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and
      will be followed for 7 days post dose. A safety review committee (SRC) will convene after the
      completion of each cohort to evaluate safety and pharmacokinetic (PK) data.

      Following the conclusion of the respective SAD level dose groups and after sufficient review
      of study data and approval by the SRC, a second set of healthy adult subjects will
      participate in an assigned MAD treatment group. The MAD treatment group is comprised of 3
      ascending dose level cohorts where subjects will be randomized to receive either PTI-808 or
      placebo daily for 7 days and will be followed for 7 days after receiving the last dose.

      Also following the conclusion of the respective SAD level dose groups, healthy adult subjects
      will participate in the FE treatment group.

      Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of
      PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive
      days.

      Part 3 will enroll adult subjects with cystic fibrosis (CF) into a MAD treatment group
      consisting of 2 cohorts. Subjects will receive PTI-808 co-administered with PTI-801 and
      PTI-428. PTI-808 will be administered daily for 7 consecutive days followed by PTI-808 +
      PTI-801 + PTI-428 administered daily for 14 consecutive days.

      Part 4 will enroll adult subjects with cystic fibrosis (CF) into 28-day cohorts. Subjects
      will receive PTI-808 co-administered with PTI-801 with or without PTI-428 versus matching
      placebo.
    

Detailed description: 
      Part 1 of this trial will enroll healthy volunteers into a single ascending dose (SAD),
      multiple ascending dose (MAD), and Food Effect (FE) treatment groups.

      The SAD treatment group is comprised of at least 3 ascending dose level cohorts where healthy
      adult subjects will be randomized to receive a single dose of either PTI-808 or placebo and
      will be followed for 7 days post dose.

      The MAD treatment group is comprised of 3 ascending dose level cohorts where subjects will be
      randomized to receive either PTI-808 or placebo daily for 7 days and will be followed for 7
      days after receiving the last dose.

      Following the conclusion of the respective SAD level dose groups the food effect portion of
      the study will be initiated and subjects will be randomized to receive an initial single dose
      of PTI-808 either after an overnight fast of at least 10 hours (fasted group) or after an
      overnight fast of at least 10 hours followed the consumption of a high fat high calorie meal
      (fed group). After a 10 day washout period, subjects will cross over to the opposite group
      and receive a second dose of PTI-808. Subjects will be followed for up to 7 days following
      dosing.

      Part 2 of this will enroll healthy volunteers to assess the safety, tolerability, and PK of
      PTI 808 co administered with PTI 801 and PTI 428 to HVs with daily dosing for 7 consecutive
      days.

      Part 3 - Part 3 will enroll adult subjects with CF to assess the safety, tolerability, and PK
      of multiple ascending doses of PTI-808 co-administered with PTI-801 and PTI-428. Subjects
      will receive 7 days of PTI-808 or placebo followed by 14 days of PTI-808 or placebo
      co-administered with PTI-801+PTI-428 or matching placebos.

      Part 4 - Part 4 will assess the safety, tolerability, PK, and the effects of PTI-808
      co-administered with PTI-801 with or without PTI-428 over a 28-day treatment period in CF
      subjects who are either homozygous for the F508del CFTR genotype or are heterozygous for the
      F508del CFTR genotype. Subjects will be randomized to receive treatment with PTI-808
      co-administered with PTI-801 with or without PTI-428 versus matching placebo.
    

Intervention name(s): PTI-808; Placebo; PTI-428; PTI-801
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Active; Placebo; Active; Active
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment