Trial Outcomes & Findings for Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and PPIX Concentrations in Participants With EPP (NCT NCT05308472)
NCT ID: NCT05308472
Last Updated: 2026-01-08
Results Overview
Percent change from baseline in PPIX concentration was analyzed using a mixed model repeated measures analysis in the ITT population.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
75 participants
Primary outcome timeframe
121 days
Results posted on
2026-01-08
Participant Flow
Participant milestones
| Measure |
Placebo
Placebo: Oral dose, once a day for 120 days
|
DISC-1459 Oral Low Dose
DISC-1459: Oral 20 mg, once a day for 120 days
|
DISC-1459 Oral High Dose
DISC-1459: Oral 60 mg, once a day for 120 days
|
|---|---|---|---|
|
Overall Study
STARTED
|
24
|
26
|
25
|
|
Overall Study
COMPLETED
|
24
|
26
|
22
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
3
|
Reasons for withdrawal
| Measure |
Placebo
Placebo: Oral dose, once a day for 120 days
|
DISC-1459 Oral Low Dose
DISC-1459: Oral 20 mg, once a day for 120 days
|
DISC-1459 Oral High Dose
DISC-1459: Oral 60 mg, once a day for 120 days
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
3
|
Baseline Characteristics
Study of Bitopertin to Evaluate the Safety, Tolerability, Efficacy, and PPIX Concentrations in Participants With EPP
Baseline characteristics by cohort
| Measure |
Placebo
n=24 Participants
Placebo: Oral dose, once a day for 120 days
|
DISC-1459 Oral Low Dose Level
n=26 Participants
DISC-1459: Oral 20 mg dose, once a day for 120 days
|
DISC-1459 Oral High Dose Level
n=25 Participants
DISC-1459: Oral 60 mg dose, once a day for 120 days
|
Total
n=75 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
Age
|
42.3 years
STANDARD_DEVIATION 12.24 • n=18 Participants
|
45.0 years
STANDARD_DEVIATION 14.31 • n=17 Participants
|
47.8 years
STANDARD_DEVIATION 14.02 • n=35 Participants
|
45.1 years
STANDARD_DEVIATION 13.58 • n=42 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=18 Participants
|
14 Participants
n=17 Participants
|
12 Participants
n=35 Participants
|
38 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=18 Participants
|
12 Participants
n=17 Participants
|
13 Participants
n=35 Participants
|
37 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=18 Participants
|
0 Participants
n=17 Participants
|
2 Participants
n=35 Participants
|
4 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=18 Participants
|
26 Participants
n=17 Participants
|
23 Participants
n=35 Participants
|
71 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=18 Participants
|
0 Participants
n=17 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=42 Participants
|
|
Whole Blood Metal-free PPIX
|
8691.0 ng/mL
STANDARD_DEVIATION 424.56 • n=18 Participants
|
8154.6 ng/mL
STANDARD_DEVIATION 6816.49 • n=17 Participants
|
10597.0 ng/mL
STANDARD_DEVIATION 4916.24 • n=35 Participants
|
9140.4 ng/mL
STANDARD_DEVIATION 5544.78 • n=42 Participants
|
PRIMARY outcome
Timeframe: 121 daysPercent change from baseline in PPIX concentration was analyzed using a mixed model repeated measures analysis in the ITT population.
Outcome measures
| Measure |
Placebo
n=24 Participants
Placebo: Oral dose, once a day for 120 days
|
DISC-1459 Oral Low Dose
n=26 Participants
DISC-1459: Oral 20 mg dose, once a day for 120 days
|
DISC-1459 Oral High Dose l
n=25 Participants
DISC-1459: Oral 60 mg dose, once a day for 120 days
|
|---|---|---|---|
|
Percent Change From Baseline in Whole Blood Metal-free PPIX Levels
|
8.07 Percent Change
Interval -6.2 to 22.338
|
-21.48 Percent Change
Interval -35.842 to -7.125
|
-41.74 Percent Change
Interval -56.531 to -26.95
|
SECONDARY outcome
Timeframe: 121 daysCumulative total hours of sunlight exposure on days with no pain from 1000 to 1800 hours from baseline to Day 121 (EOS) was analyzed using analysis of variance in the ITT population.
Outcome measures
| Measure |
Placebo
n=24 Participants
Placebo: Oral dose, once a day for 120 days
|
DISC-1459 Oral Low Dose
n=26 Participants
DISC-1459: Oral 20 mg dose, once a day for 120 days
|
DISC-1459 Oral High Dose l
n=25 Participants
DISC-1459: Oral 60 mg dose, once a day for 120 days
|
|---|---|---|---|
|
Total Hours of Sunlight Exposure to Skin on Days With no Pain From 1000 to 1800 Hours (10:00am to 6:00pm)
|
133.91 Hours
Interval 92.18 to 175.643
|
175.11 Hours
Interval 134.723 to 215.489
|
153.14 Hours
Interval 111.699 to 194.585
|
SECONDARY outcome
Timeframe: 121 daysParticipants exposed their skin to sunlight once a week and measured the time it takes to experience a prodrome. The time (minutes) to first prodromal symptom (e.g., burning, tingling, itching, or stinging) associated with sunlight exposure was recorded in a diary. This sun exposure challenge was performed weekly. The average time (minutes) to first prodromal symptom (e.g., burning, tingling, itching, or stinging) associated with sunlight exposure was averaged over two-week intervals through Study Day 121.
Outcome measures
| Measure |
Placebo
n=20 Participants
Placebo: Oral dose, once a day for 120 days
|
DISC-1459 Oral Low Dose
n=22 Participants
DISC-1459: Oral 20 mg dose, once a day for 120 days
|
DISC-1459 Oral High Dose l
n=20 Participants
DISC-1459: Oral 60 mg dose, once a day for 120 days
|
|---|---|---|---|
|
Daily Sunlight Exposure Time (Minutes) to First Prodromal Symptom (Burning, Tingling, Itching, or Stinging) Associated With Sunlight Exposure Between 1 Hour Post-sunrise and 1 Hour Pre-sunset
|
149.05 Minutes/Two Weeks
Standard Deviation 116.434
|
155.51 Minutes/Two Weeks
Standard Deviation 99.903
|
176.14 Minutes/Two Weeks
Standard Deviation 134.952
|
SECONDARY outcome
Timeframe: Sum of Day 1 to Day 121The maximum total daily pain intensity scores of phototoxic reactions over the entire treatment period (D1-D121). The maximum pain score of a phototoxic reaction was measured on a Likert Scale (0-10). Total scores range from 0-1210. A score of "0" is the best outcome; and higher scores are a worse outcome. The maximum pain values on a scale of 0-10 in a day were summed across 121 days.
Outcome measures
| Measure |
Placebo
n=24 Participants
Placebo: Oral dose, once a day for 120 days
|
DISC-1459 Oral Low Dose
n=26 Participants
DISC-1459: Oral 20 mg dose, once a day for 120 days
|
DISC-1459 Oral High Dose l
n=25 Participants
DISC-1459: Oral 60 mg dose, once a day for 120 days
|
|---|---|---|---|
|
Total Pain Intensity
|
13.0 Scores on a scale
Standard Deviation 9.38
|
15.0 Scores on a scale
Standard Deviation 13.95
|
6.3 Scores on a scale
Standard Deviation 2.50
|
SECONDARY outcome
Timeframe: 121 daysPopulation: Number and Proportion of Participants with at Least One TEAE
Incidence of treatment-emergent adverse events
Outcome measures
| Measure |
Placebo
n=24 Participants
Placebo: Oral dose, once a day for 120 days
|
DISC-1459 Oral Low Dose
n=26 Participants
DISC-1459: Oral 20 mg dose, once a day for 120 days
|
DISC-1459 Oral High Dose l
n=25 Participants
DISC-1459: Oral 60 mg dose, once a day for 120 days
|
|---|---|---|---|
|
Incidence of Treatment-emergent Adverse Events
|
19 Participants
|
19 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: 121 daysPopulation: Intention-to-treat population analyzed
Percent change from baseline in erythrocyte total PPIX concentration was summarized by analysis visit in the ITT population.
Outcome measures
| Measure |
Placebo
n=20 Participants
Placebo: Oral dose, once a day for 120 days
|
DISC-1459 Oral Low Dose
n=19 Participants
DISC-1459: Oral 20 mg dose, once a day for 120 days
|
DISC-1459 Oral High Dose l
n=17 Participants
DISC-1459: Oral 60 mg dose, once a day for 120 days
|
|---|---|---|---|
|
Erythrocyte Total PPIX Concentrations
|
19.3 Percent Change
Standard Deviation 59.95
|
-20.5 Percent Change
Standard Deviation 29.73
|
-39.9 Percent Change
Standard Deviation 34.67
|
SECONDARY outcome
Timeframe: 121 daysPopulation: Intention-to-treat population analyzed
Percent change from baseline in plasma total PPIX concentration was summarized by analysis visit in the ITT population.
Outcome measures
| Measure |
Placebo
n=18 Participants
Placebo: Oral dose, once a day for 120 days
|
DISC-1459 Oral Low Dose
n=18 Participants
DISC-1459: Oral 20 mg dose, once a day for 120 days
|
DISC-1459 Oral High Dose l
n=13 Participants
DISC-1459: Oral 60 mg dose, once a day for 120 days
|
|---|---|---|---|
|
Plasma Total PPIX Concentrations
|
11.7 Percent Change
Standard Deviation 56.76
|
-45.4 Percent Change
Standard Deviation 23.86
|
-53.9 Percent Change
Standard Deviation 31.55
|
SECONDARY outcome
Timeframe: 121 daysPopulation: Intention-to-treat population analyzed
Percent change from baseline in whole blood total PPIX concentration was summarized by analysis visit in the ITT population.
Outcome measures
| Measure |
Placebo
n=24 Participants
Placebo: Oral dose, once a day for 120 days
|
DISC-1459 Oral Low Dose
n=25 Participants
DISC-1459: Oral 20 mg dose, once a day for 120 days
|
DISC-1459 Oral High Dose l
n=18 Participants
DISC-1459: Oral 60 mg dose, once a day for 120 days
|
|---|---|---|---|
|
Whole Blood Total PPIX Concentrations
|
8.2 Percent Change
Standard Deviation 41.19
|
-19.7 Percent Change
Standard Deviation 31.71
|
-40.1 Percent Change
Standard Deviation 28.89
|
SECONDARY outcome
Timeframe: Day 29Population: Intention-to-treat population analyzed. There is no measurable bitopertin concentrations in placebo patients, since they did not receive drug.
Day 29 plasma bitopertin concentrations, 4 hours post-dose
Outcome measures
| Measure |
Placebo
n=26 Participants
Placebo: Oral dose, once a day for 120 days
|
DISC-1459 Oral Low Dose
n=25 Participants
DISC-1459: Oral 20 mg dose, once a day for 120 days
|
DISC-1459 Oral High Dose l
DISC-1459: Oral 60 mg dose, once a day for 120 days
|
|---|---|---|---|
|
Plasma Bitopertin Concentrations
|
207.3 ng/mL
Standard Deviation 83.5
|
683.4 ng/mL
Standard Deviation 308.8
|
—
|
Adverse Events
Placebo
Serious events: 1 serious events
Other events: 19 other events
Deaths: 0 deaths
DISC-1459 Oral Low Dose Level
Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths
DISC-1459 Oral High Dose Level
Serious events: 0 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=24 participants at risk
Placebo: Oral dose, once a day for 121 days
|
DISC-1459 Oral Low Dose Level
n=26 participants at risk
DISC-1459: Oral 20 mg dose, once a day for 121 days
|
DISC-1459 Oral High Dose Level
n=25 participants at risk
DISC-1459: Oral 60 mg dose, once a day for 121 days
|
|---|---|---|---|
|
Gastrointestinal disorders
acute biliary pancreatitis
|
4.2%
1/24 • Number of events 1 • 121 days
|
0.00%
0/26 • 121 days
|
0.00%
0/25 • 121 days
|
Other adverse events
| Measure |
Placebo
n=24 participants at risk
Placebo: Oral dose, once a day for 121 days
|
DISC-1459 Oral Low Dose Level
n=26 participants at risk
DISC-1459: Oral 20 mg dose, once a day for 121 days
|
DISC-1459 Oral High Dose Level
n=25 participants at risk
DISC-1459: Oral 60 mg dose, once a day for 121 days
|
|---|---|---|---|
|
General disorders
Fatigue
|
12.5%
3/24 • Number of events 3 • 121 days
|
7.7%
2/26 • Number of events 2 • 121 days
|
0.00%
0/25 • 121 days
|
|
Investigations
Aspartate aminotransferase increased
|
4.2%
1/24 • Number of events 1 • 121 days
|
3.8%
1/26 • Number of events 1 • 121 days
|
8.0%
2/25 • Number of events 2 • 121 days
|
|
Investigations
Blood iron increased
|
0.00%
0/24 • 121 days
|
7.7%
2/26 • Number of events 2 • 121 days
|
12.0%
3/25 • Number of events 3 • 121 days
|
|
Investigations
Transferrin saturation increased
|
0.00%
0/24 • 121 days
|
7.7%
2/26 • Number of events 2 • 121 days
|
8.0%
2/25 • Number of events 2 • 121 days
|
|
Nervous system disorders
Dizziness
|
12.5%
3/24 • Number of events 3 • 121 days
|
15.4%
4/26 • Number of events 4 • 121 days
|
44.0%
11/25 • Number of events 11 • 121 days
|
|
Nervous system disorders
Headache
|
12.5%
3/24 • Number of events 3 • 121 days
|
11.5%
3/26 • Number of events 3 • 121 days
|
8.0%
2/25 • Number of events 2 • 121 days
|
|
Gastrointestinal disorders
Nausea
|
16.7%
4/24 • Number of events 4 • 121 days
|
3.8%
1/26 • Number of events 1 • 121 days
|
16.0%
4/25 • Number of events 4 • 121 days
|
|
Investigations
Alanine aminotransferase increased
|
12.5%
3/24 • Number of events 3 • 121 days
|
3.8%
1/26 • Number of events 1 • 121 days
|
8.0%
2/25 • Number of events 2 • 121 days
|
|
Gastrointestinal disorders
Diarrhoea
|
8.3%
2/24 • Number of events 2 • 121 days
|
3.8%
1/26 • Number of events 1 • 121 days
|
4.0%
1/25 • Number of events 1 • 121 days
|
|
Infections and infestations
COVID-19
|
8.3%
2/24 • Number of events 2 • 121 days
|
7.7%
2/26 • Number of events 2 • 121 days
|
4.0%
1/25 • Number of events 1 • 121 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60