Digestive System Disease
Conditions
Brief summary
It is hoped that different forms of the same medicine, called PVP001, PVP002, and PVP003, will help people with celiac disease. Both healthy adults and adults with celiac disease will take part in this study. There are many main aims of the study. * To check if participants have side effects from different forms of the study medicine. These forms are called PVP001 (liquid in a cup), PVP002 capsule, and PVP003 tablet. * To check how well PVP003 breaks down gluten. * To check how much PVP003 participants can take without getting side effects from it. The study is in 4 parts. At the start of each part of the study, the study doctor will check to determine who can take part at the first study visit. Different groups of participants will be in different parts of the study. In all parts of the study, some participants will take 1 of the 3 forms of study medicine. Others will take a placebo. In this study, a placebo will look like the form of study medicine but will not have any medicine in it. This means that a placebo can either look like PVP001 liquid in a cup, the PVP002 tablet, or the PVP003 tablet. In Part 1, different small groups of participants will take lower to higher doses of PVP001 or PVP002 or a placebo. This is to work out the best dose of study medicine to take in other parts of the study. After treatment, participants will regularly visit the clinic to check that they have no problems with their treatment, including any side effects from their treatment. In Part 2, different small groups will take different doses of PVP001 or PVP002 or a placebo, either with or without a meal that has different amounts of gluten in it. This is to check if PVP001 or PVP002 has broken down gluten in the body. Participants will visit the clinic after treatment to check how much gluten has been broken down in the body. In Part 3, different small groups will take different doses of PVP003 or a placebo, either with or without a meal that has gluten in it. This is to check if PVP003 has broken down gluten in the body. Participants will visit the clinic after treatment to check if more gluten has broken down in the body. In Part 4, different small groups will take PVP003 or placebo 3 times a day for 5 days. After treatment, participants will visit the clinic to check that they have no problems with their treatment, including any side effects from their treatment.
Detailed description
This study has four parts. Each part of the study begins with a Screening Period of up to 4 weeks to allow for completion of screening procedures and subject scheduling. Each participant will be screened by means of medical history, medication review, Gastrointestinal Symptoms Questionnaire (GSQ), physical examination, vital signs, weight, height, laboratory tests, and ECG. The GSQ is being used as a separate safety monitoring tool in this study to ensure that all gastrointestinal complaints are reported by the participant. Following completion of all screening procedures, eligible participants will be enrolled in the study. Part 1 of the study in healthy participants will be completed prior to enrollment of any subject in Part 2 of the study. A participant enrolled in Part 1 of the study will participate in one of five dose Cohorts. Enrollment of healthy participants and participants with CeD in each of the five dose Cohorts will occur sequentially, but each of these dose Cohorts will be open to enrollment only after demonstration of the safety and tolerability of the same dose level in healthy participants. A healthy participant enrolled in Part 2 of the study will participate in one of three groups; within Groups 1, 2 and 3 enrollment may occur in parallel. A healthy participant enrolled in Part 3 of the study will participate in one of five groups; within Groups 1 to 5 enrollment will occur sequentially. A healthy participant enrolled in Part 4 of the study will participate in two cohorts; enrollment in Part 4 may occur in parallel with enrollment in Part 3. Each participant will be randomized to one of two possible treatment order. Participants who participate in Part 1 or Part 2 of the study, and who are not ADA positive, may participate in Part 3 or Part 4 of the study. No other participants may participate in more than one Part/Group of the study.
Interventions
OTHERPvP001 placebo
placebo
DRUGPvP001 100 mg
PvP001 100 mg
DRUGPvP001 300 mg
PvP001 300 mg
DRUGPvP001 900 mg
PvP001 900 mg
DRUGMaximum Feasible Dose (MFD) of PvP002
MFD of PvP002
DRUGMaximum Tolerated Dose (MTD) of PvP001
Maximum Tolerated Dose (MTD) of PvP001
DRUGMTD of PvP001 following 7 days of PPI treatment
Maximum Tolerated Dose (MTD) of PvP001 following 7 days of PPI (Proton Pump Inhibitor) treatment
OTHERPvP002 placebo
Placebo
DRUGPvP001 600 mg
PvP001 600 mg
DRUGPvP003 placebo
Placebo tablet orally.
DRUGPvP003
PvP003 tablet orally.
DRUGPvP003 150 mg
PvP003 150 mg
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
Part 1, Part 2, Part 3 and Part 4 1. Male or female age 18- 64 years, inclusive 2. No relevant gastrointestinal symptoms 3. Able to abstain from alcohol for 72 hours prior to the Screening Visit; for 72 hours prior to and after the Cohort Treatment Day (Part 1, Part 2, and Part 3); for 72 hours prior to the Safety Visit (Part 2 and Part 3); and for 72 hours prior to Day 1 of the first Cohort Treatment Period through the Safety Visit (Part 4). 4. A female participant must have a negative pregnancy test at Screening and on Cohort Treatment Day -1 (Part 1, Part 2, and Part 3) or a negative pregnancy test at Screening and on Day -1 of each Cohort Treatment Period (Part 4), and must agree to continue acceptable birth control measures (example, abstinence, a stable hormonal contraceptive, double-barrier method, or vasectomy in partner) from the Screening Visit through the 28 ± 2 days. Follow Up ADA Blood Sampling Visit 5. A male participant must agree to use acceptable birth control measures (e.g., abstinence, latex condom, or vasectomy), or must have a female partner who will continue birth control measures (e.g., abstinence, a stable hormonal contraceptive, or double-barrier method) from the Screening Visit through the 28 ± 2 days Follow Up Anti-Drug Antibody Blood Sampling Visit 6. Able to read and understand English 7. Able to provide written informed consent Additional Inclusion Criteria for Part 1, Part 2, Part 3, and Part 4 Healthy Adult Volunteers 8. No use of over-the-counter or prescription medication, except for birth control medications for the duration of the study 9. No history of gastrointestinal diseases or disorders 10. No history of intolerance, sensitivity, or reactions to gluten or any other food or food ingredient 11. Able to maintain a gluten-free diet for 24 hours prior to the Cohort Treatment Day (Part 1, Part 2, and Part 3), or usually ingests meals three times a day (that is, breakfast, lunch, and dinner) and is able to continue doing so during each Cohort Treatment Period (Part 4) Additional Inclusion Criteria for Part 1 Participants with Celiac Disease 12. Documented history of Celiac Disease in medical records 13. Maintaining a gluten-free diet for ≥6 months 14. No use of over-the-counter or prescription medication, except for birth control medications and those allowed by the study doctor, for the duration of the study. 15. No history of gastrointestinal diseases or disorders, other than Celiac Disease 16. No history of intolerance, hypersensitivity, or reaction to any food or food ingredient 17. Able to continue a gluten-free diet for the duration of the study
Exclusion criteria
Part 1, Part 2, Part 3, and Part 4 1. Current symptoms or signs of illness 2. Chronic viral infection or immunodeficiency condition 3. Any female who is pregnant, planning to become pregnant during the study, or breast-feeding; any male who is planning to father a child during the study 4. Receipt (or planned receipt) of another investigational medication within 4 weeks prior to the Screening Visit through the duration of the study 5. Alcohol consumption greater than (\>) 5 drinks/week, alcohol consumption within 72 hours prior to any study visit (Part 1, Part 2, and Part 3), alcohol consumption within 72 hours prior to Day 1 of the first Cohort Treatment Period through the Safety Visit (Part 4), or a positive alcohol breathalyzer test at any study visit 6. History of illicit or recreational drug use within the three years prior to the Screening Visit, or a positive urine drug screen at any study visit 7. Use of tobacco or nicotine products, including smoking, smokeless tobacco, e-cigarettes, or nicotine replacement products within 12 months prior to the Screening Visit through the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002 | Cohort Treatment Day up to 5 days after 24-hour safety assessment on Day 2 (up to Day 7) | — |
| Part 4: Number of Participants Reporting One or More TEAEs for PvP003 After Multiple Doses | Day 1 of Cohort Treatment Period 1 up to 5 days after the Day 5 of Cohort Treatment Period 2 (up to Day 28) | — |
| Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002 | Cohort Treatment Day up to 5 days after 24-hour safety assessment on Day 2 (up to Day 7) | — |
| Part 4: Number of Participants Reporting One or More TESAEs for PvP003 600 mg After Multiple Doses | Day 1 of Cohort Treatment Period 1 up to 5 days after the Day 5 of Cohort Treatment Period 2 (up to Day 28) | — |
| Part 2, Group 1, Cohort 2B: Median Percentage of Gluten Degradation by PvP001 in a Standardized 3 Gram (gm) Gluten-containing Study Meal After Administration of PvP001 | Cohort Treatment Day | Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using Enzyme-Linked Immunosorbent Assay (ELISA) based on the monoclonal R5 and G12 antibodies. |
| Part 2, Group 2, Cohort 2E: Median Percentage of Gluten Degradation by PvP002 in a Standardized 3 gm Gluten-containing Study Meal After Administration of PvP002 | Cohort Treatment Day | Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies. |
| Part 2, Group 1, Cohort 2C: Median Percentage of Gluten Degradation by PvP001 in a Standardized 3 gm Gluten-containing Study Meal Following 7 Days of Standard Dose PPI Treatment | Cohort Treatment Day | Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies. |
| Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 20 Minutes After Administration of PvP001 | Cohort Treatment Day: at 20 minutes post-dose | Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies. |
| Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP001 | Cohort Treatment Day: at 35 minutes post-dose | Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies. |
| Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP001 | Cohort Treatment Day: at 65 minutes post-dose | Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies. |
| Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 20 Minutes After Administration of PvP001 | Cohort Treatment Day: at 20 minutes post-dose | Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies. |
| Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP001 | Cohort Treatment Day: at 35 minutes post-dose | Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies. |
| Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP001 | Cohort Treatment Day: at 65 minutes post-dose | Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies. |
| Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003 | Cohort Treatment Day: at 35 minutes | Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies. |
| Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003 | Cohort Treatment Day: at 65 minutes | Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 4, Cmax: Maximum Observed Plasma Concentration for PvP003 600 mg Multiple Dose | Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose | — |
| Part 4, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP003 600 mg Multiple Dose | Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose | — |
| Part 4, T(1/2): Terminal Disposition Phase Half-life of PvP003 600 mg Multiple Dose | Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose | — |
| Part 1 and Part 2, Cmax: Maximum Observed Plasma Concentration for PvP001 and PvP002 | Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose | — |
| Part 4, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP003 600 mg Multiple Dose | Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose | — |
| Part 4: Number of Participants With ADA for PvP003 600 mg Multiple Dose | At Day 14 and Day 28 | — |
| Part 4, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for PvP003 600 mg Multiple Dose | Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose | — |
| Part 1 and Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP001 and PvP002 | Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose | — |
| Part 1 and Part 2, T(1/2): Terminal Disposition Phase Half-life of PvP001 and PvP002 | Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose | — |
| Part 1 and Part 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for PvP001 and PvP002 | Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose | — |
| Part 1 and Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP001 and PvP002 | Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose | — |
| Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | At Day 14 and Day 28 | — |
| Part 1: Maximum Tolerated Dose (MTD) of PvP001 | Cohort Treatment Day up to Day 7 | MTD was defined as the maximum dose that was determined to be safe and tolerable for Part 1 (1B-1 and 1B-2, 1C-1 and 1C-2, 1D-1 and 1D-2) in healthy or CeD participants. |
| Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | Cohort Treatment Day up to 5 days after the final Cohort Treatment Day (up to Day 22) | — |
| Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | Cohort Treatment Day up to 5 days after final Cohort Treatment Day (up to Day 10) | — |
| Part 3, Cmax: Maximum Observed Plasma Concentration for PvP003 150 mg and 600 mg Single Dose | Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose | — |
| Part 3, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP003 150 mg and 600 mg Single Dose | Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post dose | — |
| Part 3, T(1/2): Terminal Disposition Phase Half-life of PvP003 150 mg and 600 mg Single Dose | Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post dose | — |
| Part 3, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for PvP003 150 mg and 600 mg Single Dose | Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post dose | — |
| Part 3, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP003 150 mg and 600 mg Single Dose | Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post dose | — |
| Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | At Day 14 and Day 28 | — |
Countries
United States
Participant flow
Recruitment details
Participants took part in this study at 1 investigative site in the United States from 19 June 2018 to 02 July 2021.
Pre-assignment details
Healthy participants and participants with Celiac Disease (CeD) were enrolled in this 4-part study. In Part 1, healthy participants and participants with CeD were enrolled and in Parts 2, 3 and 4 only healthy participants were enrolled to receive PVP001 (TAK-062 liquid), PVP002 (TAK-062 capsule), and PVP003 (TAK-062 tablet) formulation or matching-placebo.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, (1A-1): PvP001 Placebo PvP001 (TAK-062 liquid formulation) placebo-matching liquid, orally, single dose on Cohort Treatment Day in healthy participants. | 3 |
| Part 1, (1B-1): PvP001 100 mg PvP001 (TAK-062 liquid formulation) 100 mg, orally, single dose on Cohort Treatment Day in healthy participants. | 3 |
| Part 1, (1C-1): PvP001 300 mg PvP001 (TAK-062 liquid formulation) 300 mg, orally, single dose on Cohort Treatment Day in healthy participants. | 3 |
| Part 1, (1D-1): PvP001 900 mg PvP001 (TAK-062 liquid formulation) 900 mg, orally, single dose on Cohort Treatment Day in healthy participants. | 3 |
| Part 1, (1E-1): PvP002 600 mg PvP002 (TAK-062 capsule formulation) 600 mg, orally, single dose on Cohort Treatment Day in healthy participants. | 3 |
| Part 1, (1A-2): PvP001 Placebo PvP001 (TAK-062 liquid formulation) placebo-matching liquid, orally, single dose on Cohort Treatment Day in CeD participants. | 3 |
| Part 1, (1B-2): PvP001 100 mg PvP001 (TAK-062 liquid formulation) 100 mg, orally, single dose on Cohort Treatment Day in CeD participants. | 3 |
| Part 1, (1C-2): PvP001 300 mg PvP001 (TAK-062 liquid formulation) 300 mg, orally, single dose on Cohort Treatment Day in CeD participants. | 3 |
| Part 1, (1D-2): PvP001 900 mg PvP001 (TAK-062 liquid formulation) 900 mg, orally, single dose on Cohort Treatment Day in CeD participants. | 3 |
| Part 1, (1E-2): PvP002 600 mg PvP002 (TAK-062 capsule formulation) 600 mg, orally, single dose on Cohort Treatment Day in CeD participants. | 1 |
| Part 2, Group 1: PvP001 Placebo (2A) + PvP001 900 mg (2B) + PvP001 900 mg With PPI (2C) PvP001 (TAK-062 liquid formulation) placebo-matching liquid (2A), orally, single dose on Cohort Treatment Day of Cohort 2A, followed by PvP001 900 mg (2B), orally, single dose on Cohort Treatment Day of Cohort 2B, further followed by PvP001 900 mg following 7 days of PPI treatment (2C), orally, single dose on Cohort Treatment Day of Cohort 2C in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 3 |
| Part 2, Group 1: PvP001 Placebo (2A) + PvP001 900 mg With PPI (2C) + PvP001 900 mg (2B) PvP001 (TAK-062 liquid formulation) placebo-matching liquid (2A), orally, single dose on Cohort Treatment Day of Cohort 2A, PvP001 900 mg following 7 days of PPI treatment (2C), orally, single dose on Cohort Treatment Day of Cohort 2C further followed by PvP001 900 mg (2B), orally, single dose on Cohort Treatment Day of Cohort 2B, in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 3 |
| Part 2, Group 1: PvP001 900 mg (2B) + PvP001 Placebo (2A) + PvP001 900 mg With PPI (2C) PvP001 (TAK-062 liquid formulation) 900 mg (2B), orally, single dose on Cohort Treatment Day of Cohort 2B, followed by PvP001 placebo-matching liquid (2A), orally, single dose on Cohort Treatment Day of Cohort 2A, further followed by PvP001 900 mg following 7 days of PPI treatment (2C), orally, single dose on Cohort Treatment Day of Cohort 2C in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 2 |
| Part 2, Group 1: PvP001 900 mg (2B) + PvP001 900 mg With PPI (2C) + PvP001 Placebo (2A) PvP001 (TAK-062 liquid formulation) 900 mg (2B), orally, single dose on Cohort Treatment Day of Cohort 2B, followed by PvP001 placebo-matching liquid (2A), orally, single dose on Cohort Treatment Day of Cohort 2A, further followed by PvP001 900 mg following 7 days of PPI treatment (2C), orally, single dose on Cohort Treatment Day of Cohort 2C in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 2 |
| Part 2, Group 1: PvP001 900 mg With PPI (2C) + PvP001 Placebo (2A) + PvP001 900 mg (2B) PvP001 (TAK-062 liquid formulation) 900 mg following 7 days of PPI treatment (2C), orally, single dose on Cohort Treatment Day of Cohort 2C, followed by PvP001 placebo-matching liquid (2A), orally, single dose on Cohort Treatment Day of Cohort 2A, further followed by PvP001 900 mg (2B), orally, single dose on Cohort Treatment Day of Cohort 2B in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 2 |
| Part 2, Group 1: PvP001 900 mg With PPI (2C) + PvP001 900 mg (2B) + PvP001 Placebo (2A) PvP001 (TAK-062 liquid formulation) 900 mg following 7 days of PPI treatment (2C), orally, single dose on Cohort Treatment Day of Cohort 2C, followed by PvP001 900 mg (2B), orally, single dose on Cohort Treatment Day of Cohort 2B, further followed by PvP001 placebo-matching liquid (2A), orally, single dose on Cohort Treatment Day of Cohort 2A in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 2 |
| Part 2, Group 2: PvP002 Comparator (2D) + PvP002 600 mg (2E) PvP002 capsule comparator (sterile water) (2D), orally, single dose on Cohort Treatment Day of Cohort 2D, followed by PvP002 (TAK-062 capsule formulation) 600 mg (2E), orally, single dose on Cohort Treatment Day of Cohort 2E in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 4 |
| Part 2, Group 2: PvP002 600 mg (2E) + PvP002 Comparator (2D) PvP002 (TAK-062 capsule formulation) 600 mg (2E), orally, single dose on Cohort Treatment Day of Cohort 2E, followed by PvP002 capsule comparator (sterile water) (2D), orally, single dose on Cohort Treatment Day of Cohort 2D in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 5 |
| Part 2, Group 3: PvP001 Placebo (2F) + PvP001 300 mg (2G) PvP001 (TAK-062 liquid formulation) placebo-matching liquid (2F), orally, single dose on Cohort Treatment Day of Cohort 2F, followed by PvP001 300 mg (2G), orally, single dose on Cohort Treatment Day of Cohort 2G in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 4 |
| Part 2, Group 3: PvP001 300 mg (2G) + PvP001 Placebo (2F) PvP001 (TAK-062 liquid formulation) 300 mg (2G), orally, single dose on Cohort Treatment Day of Cohort 2G, followed by PvP001 placebo-matching liquid (2F), orally, single dose on Cohort Treatment Day of Cohort 2F in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 4 |
| Part 2, Group 3: PvP001 Placebo (2F) + PvP001 600 mg (2H) PvP001 (TAK-062 liquid formulation) placebo-matching liquid (2F), orally, single dose on Cohort Treatment Day of Cohort 2F, followed by PvP001 600 mg (2H), orally, single dose on Cohort Treatment Day of Cohort 2H in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 4 |
| Part 2, Group 3: PvP001 600 mg (2H) + PvP001 Placebo (2F) PvP001 (TAK-062 liquid formulation) 600 mg (2H), orally, single dose on Cohort Treatment Day of Cohort 2H, followed by PvP001 placebo-matching liquid (2F), orally, single dose on Cohort Treatment Day of Cohort 2F in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 4 |
| Part 2, Group 3: PvP001 Placebo (2I) + PvP001 900 mg (2J) PvP001 (TAK-062 liquid formulation) placebo-matching liquid (2I), orally, single dose on Cohort Treatment Day of Cohort 2I, followed by PvP001 900 mg (2J), orally, single dose on Cohort Treatment Day of Cohort 2J in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 4 |
| Part 2, Group 3: PvP001 900 mg (2J) + PvP001 Placebo (2I) PvP001 (TAK-062 liquid formulation) 900 mg (2J), orally, single dose on Cohort Treatment Day of Cohort 2J, followed by PvP001 placebo-matching liquid (2I), orally, single dose on Cohort Treatment Day of Cohort 2I in healthy participants. There was a washout period of 7 days between each Cohort Treatment Day. | 4 |
| Part 3, Group 1: PvP003 Placebo (3A) + PvP003 600 mg (3B) PvP003 (TAK-062 tablet formulation) placebo-matching tablet (3A) with pretreatment buffer solution administered prior to the PvP003 before a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3A, followed by PvP003 600 mg (3B) with pretreatment buffer solution administered prior to the PvP003 before a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3B in healthy participants. There was a washout period of 3 days between each Cohort Treatment Day. | 3 |
| Part 3, Group 1: PvP003 600 mg (3B) + PvP003 Placebo (3A) PvP003 (TAK-062 tablet formulation) 600 mg (3B) with pretreatment buffer solution administered prior to the PvP003 before a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3B, followed by PvP003 placebo-matching tablet (3A) with pretreatment buffer solution administered prior to the PvP003 before a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3A in healthy participants. There was a washout period of 3 days between each Cohort Treatment Day. | 4 |
| Part 3, Group 2: PvP003 Placebo (3C) + PvP003 600 mg (3D) PvP003 (TAK-062 tablet formulation) placebo-matching tablet (3C) without pretreatment buffer solution before a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3C, followed by PvP003 600 mg (3D) without pretreatment buffer solution before a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3D in healthy participants. There was a washout period of 3 days between each Cohort Treatment Day. | 1 |
| Part 3, Group 2: PvP003 600 mg (3D) + PvP003 Placebo (3C) PvP003 (TAK-062 tablet formulation) 600 mg (3D) without pretreatment buffer solution before a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3D, followed by PvP003 placebo-matching tablet (3C) without pretreatment buffer solution before a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3C in healthy participants. There was a washout period of 3 days between each Cohort Treatment Day. | 5 |
| Part 3, Group 3: PvP003 Placebo (3E) + PvP003 600 mg (3F) PvP003 (TAK-062 tablet formulation) placebo-matching tablet (3E) without pretreatment buffer solution administered after an approximately 50 mL portion of standardized 1 gram gluten-containing study meal and then remaining portion of the 1 gram gluten-containing study meal was ingested after administration of PvP0003 orally, single dose on Cohort Treatment Day of Cohort 3E, followed by PvP003 600 mg (3F) without pretreatment buffer solution administered after an approximately 50 mL portion of standardized 1 gram gluten-containing study meal and then remaining portion of the 1 gram gluten-containing study meal was ingested after administration of PvP0003 orally, single dose on Cohort Treatment Day of Cohort 3F in healthy participants. There was a washout period of 3 days between each Cohort Treatment Day. | 3 |
| Part 3, Group 3: PvP003 600 mg (3F) + PvP003 Placebo (3E) PvP003 (TAK-062 tablet formulation) 600 mg (3F) without pretreatment buffer solution administered after an approximately 50 mL portion of standardized 1 gram gluten-containing study meal and then remaining portion of the 1 gram gluten-containing study meal was ingested after administration of PvP0003 orally, single dose on Cohort Treatment Day of Cohort 3F, followed by PvP003 placebo-matching tablet (3E) without pretreatment buffer solution administered after an approximately 50 mL portion of standardized 1 gram gluten-containing study meal and then remaining portion of the 1 gram gluten-containing study meal was ingested after administration of PvP0003, orally, single dose on Cohort Treatment Day of Cohort 3E, in healthy participants. There was a washout period of 3 days between each Cohort Treatment Day. | 3 |
| Part 3, Group 4: PvP003 Placebo (3G) + PvP003 600 mg (3H) PvP003 (TAK-062 tablet formulation) placebo-matching tablet (3G) without pretreatment buffer solution before standardized gluten-free study meal followed by a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3G, followed by PvP003 600 mg (3H) without pretreatment buffer solution before standardized gluten-free study meal followed by a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3H in healthy participants. There was a washout period of 3 days between each Cohort Treatment Day. | 3 |
| Part 3, Group 4: PvP003 600 mg (3H) + PvP003 Placebo (3G) PvP003 (TAK-062 tablet formulation) 600 mg (3H) without pretreatment buffer solution before standardized gluten-free study meal followed by a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3H, followed by PvP003 placebo-matching tablet (3G) without pretreatment buffer solution before standardized gluten-free study meal followed by a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3G, in healthy participants. There was a washout period of 3 days between each Cohort Treatment Day. | 3 |
| Part 3, Group 5: PvP003 Placebo (3I) + PvP003 150 mg (3J) PvP003 (TAK-062 tablet formulation) placebo-matching tablet (3I) without pretreatment buffer solution before a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3I, followed by PvP003 150 mg (3J) without pretreatment buffer solution before a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3J in healthy participants. There was a washout period of 3 days between each Cohort Treatment Day. | 5 |
| Part 3, Group 5: PvP003 150 mg (3J) + PvP003 Placebo (3I) PvP003 (TAK-062 tablet formulation) 150 mg (3J) without pretreatment buffer solution before a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3J, followed by PvP003 placebo-matching tablet (3I) without pretreatment buffer solution before a standardized 1 gm gluten-containing study meal, orally, single dose on Cohort Treatment Day of Cohort 3I in healthy participants. There was a washout period of 3 days between each Cohort Treatment Day. | 8 |
| Part 4: PvP003 Placebo, TID (4A) + PvP003 600 mg, TID (4B) PvP003 (TAK-062 tablet formulation) placebo-matching tablet, administered as two tablets of PvP003 placebo, orally, TID on Treatment Days 1 to 5 (4A) of Cohort Treatment Period 1, followed by PvP003 600 mg administered as two tablets of PvP003 300 mg, orally, TID on Treatment Days 1 to 5 (4B) of Cohort Treatment Period 2 in healthy participants. There was a washout period of 3 days between the two Cohort Treatment Periods. | 3 |
| Part 4: PvP003 600 mg, TID (4B) + PvP003 Placebo, TID (4A) PvP003 (TAK-062 tablet formulation) 600 mg, administered as two tablets of PvP003 300 mg, orally, TID on Treatment Days 1 to 5 (4B) of Cohort Treatment Period 1, followed by PvP003 placebo-matching tablet, administered as two tablets of PvP003 placebo, orally, TID on Treatment Days 1 to 5 (4A) of Cohort Treatment Period 2 in healthy participants. There was a washout period of 3 days between the two Cohort Treatment Periods. | 3 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 | FG022 | FG023 | FG024 | FG025 | FG026 | FG027 | FG028 | FG029 | FG030 | FG031 | FG032 | FG033 | FG034 | FG035 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 2 (Day 1) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2 (Day 1) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 0 | 1 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2 (Day 1) | Subject Non-compliance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 3 (Day 1) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 |
| Part 3 (Day 1) | Subject Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 0 | 0 |
| Part 3 (Day 1) | Subject Non-compliance | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 1, (1D-2): PvP001 900 mg | Part 2, Group 2: PvP002 Comparator (2D) + PvP002 600 mg (2E) | Part 1, (1A-1): PvP001 Placebo | Total | Part 3, Group 1: PvP003 Placebo (3A) + PvP003 600 mg (3B) | Part 3, Group 2: PvP003 Placebo (3C) + PvP003 600 mg (3D) | Part 3, Group 1: PvP003 600 mg (3B) + PvP003 Placebo (3A) | Part 1, (1A-2): PvP001 Placebo | Part 2, Group 1: PvP001 900 mg (2B) + PvP001 900 mg With PPI (2C) + PvP001 Placebo (2A) | Part 2, Group 1: PvP001 Placebo (2A) + PvP001 900 mg (2B) + PvP001 900 mg With PPI (2C) | Part 4: PvP003 Placebo, TID (4A) + PvP003 600 mg, TID (4B) | Part 3, Group 5: PvP003 150 mg (3J) + PvP003 Placebo (3I) | Part 2, Group 2: PvP002 600 mg (2E) + PvP002 Comparator (2D) | Part 1, (1B-1): PvP001 100 mg | Part 2, Group 1: PvP001 Placebo (2A) + PvP001 900 mg With PPI (2C) + PvP001 900 mg (2B) | Part 3, Group 5: PvP003 Placebo (3I) + PvP003 150 mg (3J) | Part 1, (1E-2): PvP002 600 mg | Part 2, Group 3: PvP001 Placebo (2F) + PvP001 300 mg (2G) | Part 4: PvP003 600 mg, TID (4B) + PvP003 Placebo, TID (4A) | Part 2, Group 1: PvP001 900 mg With PPI (2C) + PvP001 900 mg (2B) + PvP001 Placebo (2A) | Part 2, Group 3: PvP001 300 mg (2G) + PvP001 Placebo (2F) | Part 1, (1C-1): PvP001 300 mg | Part 2, Group 3: PvP001 Placebo (2F) + PvP001 600 mg (2H) | Part 3, Group 4: PvP003 600 mg (3H) + PvP003 Placebo (3G) | Part 2, Group 1: PvP001 900 mg (2B) + PvP001 Placebo (2A) + PvP001 900 mg With PPI (2C) | Part 1, (1D-1): PvP001 900 mg | Part 2, Group 1: PvP001 900 mg With PPI (2C) + PvP001 Placebo (2A) + PvP001 900 mg (2B) | Part 3, Group 2: PvP003 600 mg (3D) + PvP003 Placebo (3C) | Part 3, Group 4: PvP003 Placebo (3G) + PvP003 600 mg (3H) | Part 2, Group 3: PvP001 600 mg (2H) + PvP001 Placebo (2F) | Part 3, Group 3: PvP003 600 mg (3F) + PvP003 Placebo (3E) | Part 2, Group 3: PvP001 Placebo (2I) + PvP001 900 mg (2J) | Part 1, (1C-2): PvP001 300 mg | Part 1, (1E-1): PvP002 600 mg | Part 2, Group 3: PvP001 900 mg (2J) + PvP001 Placebo (2I) | Part 3, Group 3: PvP003 Placebo (3E) + PvP003 600 mg (3F) | Part 1, (1B-2): PvP001 100 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 4 Participants | 3 Participants | 119 Participants | 3 Participants | 1 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 8 Participants | 5 Participants | 3 Participants | 3 Participants | 5 Participants | 1 Participants | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 5 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 33 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 4 Participants | 3 Participants | 86 Participants | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 2 Participants | 11 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 32 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 0 Participants | 75 Participants | 1 Participants | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 5 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 3 Participants | 4 Participants | 3 Participants | 119 Participants | 3 Participants | 1 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 8 Participants | 5 Participants | 3 Participants | 3 Participants | 5 Participants | 1 Participants | 4 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 5 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 0 Participants | 44 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 3 Participants | 3 Participants | 75 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 6 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 0 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk | EG026 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 1 | 0 / 13 | 0 / 12 | 0 / 13 | 0 / 9 | 0 / 9 | 0 / 24 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 36 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 13 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 3 / 3 | 0 / 3 | 2 / 3 | 1 / 3 | 1 / 1 | 1 / 13 | 0 / 12 | 2 / 13 | 0 / 9 | 0 / 9 | 1 / 24 | 1 / 8 | 1 / 8 | 0 / 8 | 4 / 36 | 1 / 6 | 0 / 6 | 0 / 6 | 1 / 6 | 1 / 13 | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 1 | 0 / 13 | 0 / 12 | 0 / 13 | 0 / 9 | 0 / 9 | 0 / 24 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 35 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 13 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002
Time frame: Cohort Treatment Day up to 5 days after 24-hour safety assessment on Day 2 (up to Day 7)
Population: Safety population included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed only for Part 1 of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1C-1): PvP001 300 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1D-1): PvP001 900 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1E-1): PvP002 600 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1A-2): PvP001 Placebo | Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002 | 3 Participants |
| Part 1, (1B-2): PvP001 100 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1C-2): PvP001 300 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002 | 2 Participants |
| Part 1, (1D-2): PvP001 900 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002 | 1 Participants |
| Part 1, (1E-2): PvP002 600 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs) for PvP001 and PvP002 | 1 Participants |
Primary
Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002
Time frame: Cohort Treatment Day up to 5 days after 24-hour safety assessment on Day 2 (up to Day 7)
Population: Safety population included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed only for Part 1 of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1C-1): PvP001 300 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1D-1): PvP001 900 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1E-1): PvP002 600 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1A-2): PvP001 Placebo | Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1B-2): PvP001 100 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1C-2): PvP001 300 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1D-2): PvP001 900 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002 | 0 Participants |
| Part 1, (1E-2): PvP002 600 mg | Part 1: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Events (TESAEs) for PvP001 and PvP002 | 0 Participants |
Primary
Part 2, Group 1, Cohort 2B: Median Percentage of Gluten Degradation by PvP001 in a Standardized 3 Gram (gm) Gluten-containing Study Meal After Administration of PvP001
Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using Enzyme-Linked Immunosorbent Assay (ELISA) based on the monoclonal R5 and G12 antibodies.
Time frame: Cohort Treatment Day
Population: Intent-to-Treat (ITT) population in Part 2 of the study, included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed in Group 1, Cohort 2B (PvP001 900 mg) of Part 2 only. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 1, Cohort 2B: Median Percentage of Gluten Degradation by PvP001 in a Standardized 3 Gram (gm) Gluten-containing Study Meal After Administration of PvP001 | R5 | 94.41 percentage of gluten degradation |
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 1, Cohort 2B: Median Percentage of Gluten Degradation by PvP001 in a Standardized 3 Gram (gm) Gluten-containing Study Meal After Administration of PvP001 | G12 | 97.89 percentage of gluten degradation |
Primary
Part 2, Group 1, Cohort 2C: Median Percentage of Gluten Degradation by PvP001 in a Standardized 3 gm Gluten-containing Study Meal Following 7 Days of Standard Dose PPI Treatment
Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.
Time frame: Cohort Treatment Day
Population: ITT population in Part 2 of the study, included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed in Group 1, Cohort 2C (PvP001 900 mg) of Part 2 only. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 1, Cohort 2C: Median Percentage of Gluten Degradation by PvP001 in a Standardized 3 gm Gluten-containing Study Meal Following 7 Days of Standard Dose PPI Treatment | R5 | 99.44 percentage of gluten degradation |
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 1, Cohort 2C: Median Percentage of Gluten Degradation by PvP001 in a Standardized 3 gm Gluten-containing Study Meal Following 7 Days of Standard Dose PPI Treatment | G12 | 99.62 percentage of gluten degradation |
Primary
Part 2, Group 2, Cohort 2E: Median Percentage of Gluten Degradation by PvP002 in a Standardized 3 gm Gluten-containing Study Meal After Administration of PvP002
Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.
Time frame: Cohort Treatment Day
Population: ITT population in Part 2 of the study, included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed in Group 2, Cohort 2E (PvP002 600 mg) of Part 2 only. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 2, Cohort 2E: Median Percentage of Gluten Degradation by PvP002 in a Standardized 3 gm Gluten-containing Study Meal After Administration of PvP002 | R5 | 99.67 percentage of gluten degradation |
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 2, Cohort 2E: Median Percentage of Gluten Degradation by PvP002 in a Standardized 3 gm Gluten-containing Study Meal After Administration of PvP002 | G12 | 99.70 percentage of gluten degradation |
Primary
Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 20 Minutes After Administration of PvP001
Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.
Time frame: Cohort Treatment Day: at 20 minutes post-dose
Population: ITT population in Part 2 of the study, included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed in Group 3, Cohort 2G (PvP001 300 mg) and Cohort 2H (PvP001 600 mg) of Part 2 only.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 20 Minutes After Administration of PvP001 | R5: 20 minutes | 95.89 percentage of gluten degradation |
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 20 Minutes After Administration of PvP001 | G12: 20 minutes | 97.63 percentage of gluten degradation |
| Part 1, (1B-1): PvP001 100 mg | Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 20 Minutes After Administration of PvP001 | R5: 20 minutes | 98.13 percentage of gluten degradation |
| Part 1, (1B-1): PvP001 100 mg | Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 20 Minutes After Administration of PvP001 | G12: 20 minutes | 97.98 percentage of gluten degradation |
Primary
Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP001
Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.
Time frame: Cohort Treatment Day: at 35 minutes post-dose
Population: ITT population in Part 2 of the study, included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed in Group 3, Cohort 2G (PvP001 300 mg) and Cohort 2H (PvP001 600 mg) of Part 2 only.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP001 | R5: 35 minutes | 98.19 percentage of gluten degradation |
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP001 | G12: 35 minutes | 97.92 percentage of gluten degradation |
| Part 1, (1B-1): PvP001 100 mg | Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP001 | R5: 35 minutes | 98.95 percentage of gluten degradation |
| Part 1, (1B-1): PvP001 100 mg | Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP001 | G12: 35 minutes | 98.43 percentage of gluten degradation |
Primary
Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP001
Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.
Time frame: Cohort Treatment Day: at 65 minutes post-dose
Population: ITT population in Part 2 of the study, included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed in Group 3, Cohort 2G (PvP001 300 mg) and Cohort 2H (PvP001 600 mg) of Part 2 only.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP001 | R5: 65 minutes | 95.21 percentage of gluten degradation |
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP001 | G12: 65 minutes | 96.30 percentage of gluten degradation |
| Part 1, (1B-1): PvP001 100 mg | Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP001 | R5: 65 minutes | 98.15 percentage of gluten degradation |
| Part 1, (1B-1): PvP001 100 mg | Part 2, Group 3, Cohort 2G and 2H: Median Percentage of Gluten Degradation by PvP001 300 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP001 | G12: 65 minutes | 98.87 percentage of gluten degradation |
Primary
Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 20 Minutes After Administration of PvP001
Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.
Time frame: Cohort Treatment Day: at 20 minutes post-dose
Population: ITT population in Part 2 of the study, included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed in Group 3, Cohort 2J (PvP001 900 mg) of Part 2 only.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 20 Minutes After Administration of PvP001 | R5: 20 minutes | 99.82 percentage of gluten degradation |
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 20 Minutes After Administration of PvP001 | G12: 20 minutes | 99.77 percentage of gluten degradation |
Primary
Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP001
Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.
Time frame: Cohort Treatment Day: at 35 minutes post-dose
Population: ITT population in Part 2 of the study, included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed in Group 3, Cohort 2J (PvP001 900 mg) of Part 2 only.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP001 | R5: 35 minutes | 99.48 percentage of gluten degradation |
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP001 | G12: 35 minutes | 99.69 percentage of gluten degradation |
Primary
Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP001
Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.
Time frame: Cohort Treatment Day: at 65 minutes post-dose
Population: ITT population in Part 2 of the study, included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed in Group 3, Cohort 2J (PvP001 900 mg) of Part 2 only.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP001 | R5: 65 minutes | 99.22 percentage of gluten degradation |
| Part 1, (1A-1): PvP001 Placebo | Part 2, Group 3, Cohort 2J: Median Percentage of Gluten Degradation by PvP001 900 mg in a Standardized 6 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP001 | G12: 65 minutes | 98.49 percentage of gluten degradation |
Primary
Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003
Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.
Time frame: Cohort Treatment Day: at 35 minutes
Population: ITT population in Part 3 of study, included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed for Group 1, Cohort 3B (PvP003 600 mg), Group 2, Cohort 3D (PvP003 600 mg), Group 3, Cohort 3F (PvP003 600 mg), Group 4, Cohort 3H (PvP003 600 mg) and Group 5, Cohort 3J (PvP003 150 mg) of Part 3. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003 | R5: 35 minutes | 94.68 percentage of gluten degradation |
| Part 1, (1A-1): PvP001 Placebo | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003 | G12: 35 minutes | 96.66 percentage of gluten degradation |
| Part 1, (1B-1): PvP001 100 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003 | R5: 35 minutes | 79.69 percentage of gluten degradation |
| Part 1, (1B-1): PvP001 100 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003 | G12: 35 minutes | 71.71 percentage of gluten degradation |
| Part 1, (1C-1): PvP001 300 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003 | R5: 35 minutes | 68.49 percentage of gluten degradation |
| Part 1, (1C-1): PvP001 300 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003 | G12: 35 minutes | 71.11 percentage of gluten degradation |
| Part 1, (1D-1): PvP001 900 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003 | G12: 35 minutes | NA percentage of gluten degradation |
| Part 1, (1D-1): PvP001 900 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003 | R5: 35 minutes | NA percentage of gluten degradation |
| Part 1, (1E-1): PvP002 600 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003 | R5: 35 minutes | 88.23 percentage of gluten degradation |
| Part 1, (1E-1): PvP002 600 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 35 Minutes After Administration of PvP003 | G12: 35 minutes | 93.12 percentage of gluten degradation |
Primary
Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003
Median percentage degraded relative to placebo was derived using the formula: (1 - \[active/placebo\])\*100. Gluten degradation was assessed using ELISA based on the monoclonal R5 and G12 antibodies.
Time frame: Cohort Treatment Day: at 65 minutes
Population: ITT population in Part 3 of study, included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed for Group 1, Cohort 3B (PvP003 600 mg), Group 2, Cohort 3D (PvP003 600 mg), Group 3, Cohort 3F (PvP003 600 mg), Group 4,Cohort 3H (PvP003 600 mg), Group 5, Cohort 3J (PvP003 150 mg) of Part 3. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003 | R5: 65 minutes | 89.54 percentage of gluten degradation |
| Part 1, (1A-1): PvP001 Placebo | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003 | G12: 65 minutes | 95.34 percentage of gluten degradation |
| Part 1, (1B-1): PvP001 100 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003 | R5: 65 minutes | 50.36 percentage of gluten degradation |
| Part 1, (1B-1): PvP001 100 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003 | G12: 65 minutes | 64.40 percentage of gluten degradation |
| Part 1, (1C-1): PvP001 300 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003 | R5: 65 minutes | 85.63 percentage of gluten degradation |
| Part 1, (1C-1): PvP001 300 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003 | G12: 65 minutes | 85.69 percentage of gluten degradation |
| Part 1, (1D-1): PvP001 900 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003 | G12: 65 minutes | 96.34 percentage of gluten degradation |
| Part 1, (1D-1): PvP001 900 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003 | R5: 65 minutes | 98.86 percentage of gluten degradation |
| Part 1, (1E-1): PvP002 600 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003 | R5: 65 minutes | 84.48 percentage of gluten degradation |
| Part 1, (1E-1): PvP002 600 mg | Part 3, Groups 1 to 5, Cohorts 3B, 3D, 3F, 3H and 3J: Median Percentage of Gluten Degradation by PvP003 150 mg and 600 mg in a Standardized 1 gm Gluten-containing Study Meal at 65 Minutes After Administration of PvP003 | G12: 65 minutes | 92.35 percentage of gluten degradation |
Primary
Part 4: Number of Participants Reporting One or More TEAEs for PvP003 After Multiple Doses
Time frame: Day 1 of Cohort Treatment Period 1 up to 5 days after the Day 5 of Cohort Treatment Period 2 (up to Day 28)
Population: Safety population included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed only for Part 4 of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 4: Number of Participants Reporting One or More TEAEs for PvP003 After Multiple Doses | 0 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 4: Number of Participants Reporting One or More TEAEs for PvP003 After Multiple Doses | 0 Participants |
Primary
Part 4: Number of Participants Reporting One or More TESAEs for PvP003 600 mg After Multiple Doses
Time frame: Day 1 of Cohort Treatment Period 1 up to 5 days after the Day 5 of Cohort Treatment Period 2 (up to Day 28)
Population: Safety population included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed only for Part 4 of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 4: Number of Participants Reporting One or More TESAEs for PvP003 600 mg After Multiple Doses | 0 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 4: Number of Participants Reporting One or More TESAEs for PvP003 600 mg After Multiple Doses | 0 Participants |
Secondary
Part 1 and Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP001 and PvP002
Time frame: Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Parts 1 and 2 PvP001 and PvP002; however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time-points for all arms.
Secondary
Part 1 and Part 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for PvP001 and PvP002
Time frame: Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Parts 1 and 2 PvP001 and PvP002; however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time-points for all arms.
Secondary
Part 1 and Part 2, Cmax: Maximum Observed Plasma Concentration for PvP001 and PvP002
Time frame: Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose
Population: Pharmacokinetic (PK) population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Parts 1 and 2 PvP001 and PvP002; however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time-points for all arms.
Secondary
Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002
Time frame: At Day 14 and Day 28
Population: Safety population included all participants who received at least one dose of study drug. As planned, data was collected and analyzed at Day 14 and Day 28 after the final Cohort Treatment Day to test for ADA to PvP001 and PvP002; therefore, sequence-wise data is reported for Parts 1 and 2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 1, (1A-1): PvP001 Placebo | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 1, (1C-1): PvP001 300 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 1, (1C-1): PvP001 300 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 1, (1D-1): PvP001 900 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 1, (1D-1): PvP001 900 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 1, (1E-1): PvP002 600 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 1, (1E-1): PvP002 600 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 1, (1A-2): PvP001 Placebo | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 1, (1A-2): PvP001 Placebo | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 1, (1B-2): PvP001 100 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 1, (1B-2): PvP001 100 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 1, (1C-2): PvP001 300 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 1, (1C-2): PvP001 300 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 1, (1D-2): PvP001 900 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 1, (1D-2): PvP001 900 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 1, (1E-2): PvP002 600 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 1, (1E-2): PvP002 600 mg | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 2, Group 2: PvP002 Placebo (2D) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 1 Participants |
| Part 2, Group 2: PvP002 Placebo (2D) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 1 Participants |
| Part 2, Group 2: PvP002 600 mg (2E) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 2, Group 2: PvP002 600 mg (2E) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 2, Group 3: PvP001 300 mg (2G) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 1 Participants |
| Part 2, Group 3: PvP001 300 mg (2G) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 1 Participants |
| Part 2, Group 3: PvP001 600 mg (2H) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 2, Group 3: PvP001 600 mg (2H) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 2, Group 3: PvP001 900 mg (2J) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 2, Group 3: PvP001 900 mg (2J) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 2, Group 1: PvP001 900 mg With PPI (2C) + PvP001 900 mg (2B) + PvP001 Placebo (2A) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 2, Group 1: PvP001 900 mg With PPI (2C) + PvP001 900 mg (2B) + PvP001 Placebo (2A) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 2, Group 2: PvP002 Comparator (2D) + PvP002 600 mg (2E) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 2, Group 2: PvP002 Comparator (2D) + PvP002 600 mg (2E) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 2, Group 2: PvP002 600 mg (2E) + PvP002 Comparator (2D) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 2, Group 2: PvP002 600 mg (2E) + PvP002 Comparator (2D) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 2, Group 3: PvP001 Placebo (2F) + PvP001 300 mg (2G) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 2, Group 3: PvP001 Placebo (2F) + PvP001 300 mg (2G) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 2, Group 3: PvP001 300 mg (2G) + PvP001 Placebo (2F) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 2, Group 3: PvP001 300 mg (2G) + PvP001 Placebo (2F) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 2, Group 3: PvP001 Placebo (2F) + PvP001 600 mg (2H) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 2, Group 3: PvP001 Placebo (2F) + PvP001 600 mg (2H) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 2, Group 3: PvP001 600 mg (2H) + PvP001 Placebo (2F) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 2, Group 3: PvP001 600 mg (2H) + PvP001 Placebo (2F) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 2, Group 3: PvP001 Placebo (2I) + PvP001 900 mg (2J) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 2, Group 3: PvP001 Placebo (2I) + PvP001 900 mg (2J) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
| Part 2, Group 3: PvP001 900 mg (2J) + PvP001 Placebo (2I) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 14 | 0 Participants |
| Part 2, Group 3: PvP001 900 mg (2J) + PvP001 Placebo (2I) | Part 1 and Part 2: Number of Participants With Anti-drug Antibodies (ADA) for PvP001 and PvP002 | Day 28 | 0 Participants |
Secondary
Part 1 and Part 2, T(1/2): Terminal Disposition Phase Half-life of PvP001 and PvP002
Time frame: Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Parts 1 and 2 PvP001 and PvP002; however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time-points for all arms.
Secondary
Part 1 and Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP001 and PvP002
Time frame: Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Parts 1 and 2 PvP001 and PvP002; however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time-points for all arms.
Secondary
Part 1: Maximum Tolerated Dose (MTD) of PvP001
MTD was defined as the maximum dose that was determined to be safe and tolerable for Part 1 (1B-1 and 1B-2, 1C-1 and 1C-2, 1D-1 and 1D-2) in healthy or CeD participants.
Time frame: Cohort Treatment Day up to Day 7
Population: Safety population included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed only for Part 1 (1B-1 and 1B-2, 1C-1 and 1C-2, 1D-1 and 1D-2) in healthy or CeD participants of the study. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 1: Maximum Tolerated Dose (MTD) of PvP001 | 900 mg |
Secondary
Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002
Time frame: Cohort Treatment Day up to 5 days after the final Cohort Treatment Day (up to Day 22)
Population: Safety population included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed only in the Part 2 of this study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TESAEs | 0 Participants |
| Part 1, (1A-1): PvP001 Placebo | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TEAEs | 1 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TESAEs | 0 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TEAEs | 0 Participants |
| Part 1, (1C-1): PvP001 300 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TEAEs | 2 Participants |
| Part 1, (1C-1): PvP001 300 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TESAEs | 0 Participants |
| Part 1, (1D-1): PvP001 900 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TEAEs | 0 Participants |
| Part 1, (1D-1): PvP001 900 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TESAEs | 0 Participants |
| Part 1, (1E-1): PvP002 600 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TESAEs | 0 Participants |
| Part 1, (1E-1): PvP002 600 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TEAEs | 0 Participants |
| Part 1, (1A-2): PvP001 Placebo | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TESAEs | 0 Participants |
| Part 1, (1A-2): PvP001 Placebo | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TEAEs | 1 Participants |
| Part 1, (1B-2): PvP001 100 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TEAEs | 1 Participants |
| Part 1, (1B-2): PvP001 100 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TESAEs | 0 Participants |
| Part 1, (1C-2): PvP001 300 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TESAEs | 0 Participants |
| Part 1, (1C-2): PvP001 300 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TEAEs | 1 Participants |
| Part 1, (1D-2): PvP001 900 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TEAEs | 0 Participants |
| Part 1, (1D-2): PvP001 900 mg | Part 2: Number of Participants Reporting One or More TEAEs and TESAEs for PvP001 and PvP002 | TESAEs | 0 Participants |
Secondary
Part 3, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP003 150 mg and 600 mg Single Dose
Time frame: Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Part 3, PvP003 150 mg and 600 mg cohorts; however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time-points for all arms.
Secondary
Part 3, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for PvP003 150 mg and 600 mg Single Dose
Time frame: Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Part 3, PvP003 150 mg and 600 mg cohorts; however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time-points for all arms.
Secondary
Part 3, Cmax: Maximum Observed Plasma Concentration for PvP003 150 mg and 600 mg Single Dose
Time frame: Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post-dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Part 3, PvP003 150 mg and 600 mg cohorts; however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time-points for all arms.
Secondary
Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose
Time frame: Cohort Treatment Day up to 5 days after final Cohort Treatment Day (up to Day 10)
Population: Safety population included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed for Part 3 of this study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | TEAEs | 4 Participants |
| Part 1, (1A-1): PvP001 Placebo | Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | TESAEs | 0 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | TEAEs | 1 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | TESAEs | 0 Participants |
| Part 1, (1C-1): PvP001 300 mg | Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | TEAEs | 0 Participants |
| Part 1, (1C-1): PvP001 300 mg | Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | TESAEs | 0 Participants |
| Part 1, (1D-1): PvP001 900 mg | Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | TEAEs | 0 Participants |
| Part 1, (1D-1): PvP001 900 mg | Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | TESAEs | 0 Participants |
| Part 1, (1E-1): PvP002 600 mg | Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | TEAEs | 1 Participants |
| Part 1, (1E-1): PvP002 600 mg | Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | TESAEs | 0 Participants |
| Part 1, (1A-2): PvP001 Placebo | Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | TEAEs | 1 Participants |
| Part 1, (1A-2): PvP001 Placebo | Part 3: Number of Participants Reporting One or More TEAEs and TESAEs With PvP003 After a Single Dose | TESAEs | 0 Participants |
Secondary
Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose
Time frame: At Day 14 and Day 28
Population: Safety population included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed only for Part 3 of this study. As planned, data was collected and analyzed at Day 14 and Day 28 after the final Cohort Treatment Day to test for ADA to PvP003; therefore, sequence-wise data is reported for Part 3.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 14 | 0 Participants |
| Part 1, (1A-1): PvP001 Placebo | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 28 | 0 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 14 | 0 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 28 | 0 Participants |
| Part 1, (1C-1): PvP001 300 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 14 | 0 Participants |
| Part 1, (1C-1): PvP001 300 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 28 | 0 Participants |
| Part 1, (1D-1): PvP001 900 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 14 | 0 Participants |
| Part 1, (1D-1): PvP001 900 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 28 | 0 Participants |
| Part 1, (1E-1): PvP002 600 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 28 | 0 Participants |
| Part 1, (1E-1): PvP002 600 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 14 | 0 Participants |
| Part 1, (1A-2): PvP001 Placebo | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 28 | 0 Participants |
| Part 1, (1A-2): PvP001 Placebo | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 14 | 0 Participants |
| Part 1, (1B-2): PvP001 100 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 28 | 0 Participants |
| Part 1, (1B-2): PvP001 100 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 14 | 0 Participants |
| Part 1, (1C-2): PvP001 300 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 14 | 0 Participants |
| Part 1, (1C-2): PvP001 300 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 28 | 0 Participants |
| Part 1, (1D-2): PvP001 900 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 14 | 0 Participants |
| Part 1, (1D-2): PvP001 900 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 28 | 0 Participants |
| Part 1, (1E-2): PvP002 600 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 14 | 0 Participants |
| Part 1, (1E-2): PvP002 600 mg | Part 3: Number of Participants With ADA for PvP003 150 mg and 600 mg Single Dose | Day 28 | 0 Participants |
Secondary
Part 3, T(1/2): Terminal Disposition Phase Half-life of PvP003 150 mg and 600 mg Single Dose
Time frame: Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Part 3, PvP003 150 mg and 600 mg cohorts; however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time-points for all arms.
Secondary
Part 3, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP003 150 mg and 600 mg Single Dose
Time frame: Cohort Treatment Day pre-dose and at multiple time points (up to 480 minutes) post dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Part 3, PvP003 150 mg and 600 mg cohorts; however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time-points for all arms.
Secondary
Part 4, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for PvP003 600 mg Multiple Dose
Time frame: Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Part 4, PvP003 600 mg, TID (4B); however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time points for all arms.
Secondary
Part 4, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for PvP003 600 mg Multiple Dose
Time frame: Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Part 4, PvP003 600 mg, TID (4B); however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time points for all arms.
Secondary
Part 4, Cmax: Maximum Observed Plasma Concentration for PvP003 600 mg Multiple Dose
Time frame: Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Part 4, PvP003 600 mg, TID (4B); however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time-points for all arms.
Secondary
Part 4: Number of Participants With ADA for PvP003 600 mg Multiple Dose
Time frame: At Day 14 and Day 28
Population: Safety population included all participants who received at least one dose of study drug. As planned, this outcome measure was assessed only for Part 4 of this study. As planned, data was collected and analyzed at Day 14 and Day 28 after Day 5 of the second Cohort Treatment Period to test for ADA to PvP003; therefore, sequence-wise data is reported for Part 4.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, (1A-1): PvP001 Placebo | Part 4: Number of Participants With ADA for PvP003 600 mg Multiple Dose | Day 14 | 1 Participants |
| Part 1, (1A-1): PvP001 Placebo | Part 4: Number of Participants With ADA for PvP003 600 mg Multiple Dose | Day 28 | 1 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 4: Number of Participants With ADA for PvP003 600 mg Multiple Dose | Day 14 | 1 Participants |
| Part 1, (1B-1): PvP001 100 mg | Part 4: Number of Participants With ADA for PvP003 600 mg Multiple Dose | Day 28 | 0 Participants |
Secondary
Part 4, T(1/2): Terminal Disposition Phase Half-life of PvP003 600 mg Multiple Dose
Time frame: Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Part 4, PvP003 600 mg, TID (4B); however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time points for all arms.
Secondary
Part 4, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for PvP003 600 mg Multiple Dose
Time frame: Cohort Treatment Days 1 and 5 pre-dose and at multiple time points (up to 240 minutes) post dose
Population: PK population included all participants who received at least one dose of study drug and had any PK data. As planned, this outcome measure was to be assessed for Part 4, PvP003 600 mg, TID (4B); however, PK analysis was not conducted since plasma concentrations were below the LLOQ at all sampling time points for all arms.