Trial Outcomes & Findings for A Study of AT2101 (Afegostat Tartrate) in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy (NCT NCT00433147)
NCT ID: NCT00433147
Last Updated: 2018-09-25
Results Overview
TEAEs were defined as any adverse event (AE) with a start date on or after administration of the study drug (on Day 1). A severe AE was defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through 7 days after the last dose of study drug (Day 35) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
30 participants
Primary outcome timeframe
Day 1 (after dosing) through Day 35
Results posted on
2018-09-25
Participant Flow
Participants were screened for evaluation of eligibility to participate in the study. Confirmatory β-glucosidase genotype testing was done at screening to confirm reported genotype. Thirty participants received at least 1 dose of study drug. All participants were eligible for inclusion in the safety and 29 in the pharmacodynamics (PD) populations.
Participant milestones
| Measure |
Afegostat Tartrate 25 Milligrams (mg) Once Per Day
Afegostat tartrate was administered orally during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Per Day
Afegostat tartrate was administered orally once per day during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Every Four Days
Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Every Seven Days
Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
7
|
7
|
9
|
7
|
|
Overall Study
Safety Population
|
7
|
7
|
9
|
7
|
|
Overall Study
PD Population
|
7
|
6
|
9
|
7
|
|
Overall Study
Received at Least One Dose of Study Drug
|
7
|
7
|
9
|
7
|
|
Overall Study
COMPLETED
|
7
|
6
|
9
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Afegostat Tartrate 25 Milligrams (mg) Once Per Day
Afegostat tartrate was administered orally during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Per Day
Afegostat tartrate was administered orally once per day during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Every Four Days
Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Every Seven Days
Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
0
|
Baseline Characteristics
A Study of AT2101 (Afegostat Tartrate) in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy
Baseline characteristics by cohort
| Measure |
Afegostat Tartrate 25 mg Once Per Day
n=7 Participants
Afegostat tartrate was administered orally during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Per Day
n=7 Participants
Afegostat tartrate was administered orally once per day during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Every Four Days
n=9 Participants
Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Every Seven Days
n=7 Participants
Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
41.4 years
STANDARD_DEVIATION 15.1 • n=5 Participants
|
43.4 years
STANDARD_DEVIATION 18.0 • n=7 Participants
|
36.7 years
STANDARD_DEVIATION 12.0 • n=5 Participants
|
45.0 years
STANDARD_DEVIATION 12.3 • n=4 Participants
|
41.3 years
STANDARD_DEVIATION 14.01 • n=21 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1 (after dosing) through Day 35Population: Safety Population: all participants who received at least 1 dose of study drug.
TEAEs were defined as any adverse event (AE) with a start date on or after administration of the study drug (on Day 1). A severe AE was defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through 7 days after the last dose of study drug (Day 35) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
Afegostat Tartrate 25 mg Once Per Day
n=7 Participants
Afegostat tartrate was administered orally during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Per Day
n=7 Participants
Afegostat tartrate was administered orally once per day during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Every Four Days
n=9 Participants
Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Every Seven Days
n=7 Participants
Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period.
|
|---|---|---|---|---|
|
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Day 28Population: PD Population: All participants who were included in the Safety Population and had a baseline and at least 1 post-baseline PD measurement.
GCase is a biomarker used to assess the PD effects of afegostat tartrate. Blood samples were collected to assess GCase levels in WBC. The baseline value was defined as the last non-missing value before the start of study drug.
Outcome measures
| Measure |
Afegostat Tartrate 25 mg Once Per Day
n=7 Participants
Afegostat tartrate was administered orally during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Per Day
n=6 Participants
Afegostat tartrate was administered orally once per day during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Every Four Days
n=9 Participants
Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Every Seven Days
n=7 Participants
Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period.
|
|---|---|---|---|---|
|
Change From Baseline To End Of Treatment In Beta-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)
Baseline
|
8.732 pmol/mg/min
Standard Deviation 3.1079
|
8.543 pmol/mg/min
Standard Deviation 4.1560
|
9.371 pmol/mg/min
Standard Deviation 3.5133
|
12.035 pmol/mg/min
Standard Deviation 5.4742
|
|
Change From Baseline To End Of Treatment In Beta-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)
Day 28
|
19.148 pmol/mg/min
Standard Deviation 17.0210
|
23.557 pmol/mg/min
Standard Deviation 14.6970
|
14.687 pmol/mg/min
Standard Deviation 4.4901
|
13.026 pmol/mg/min
Standard Deviation 8.7286
|
|
Change From Baseline To End Of Treatment In Beta-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)
Change from Baseline to Day 28
|
10.226 pmol/mg/min
Standard Deviation 16.4000
|
15.013 pmol/mg/min
Standard Deviation 11.2934
|
4.686 pmol/mg/min
Standard Deviation 3.1759
|
-1.028 pmol/mg/min
Standard Deviation 3.8147
|
Adverse Events
Afegostat Tartrate 25 mg Once Per Day
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Afegostat Tartrate 150 mg Once Per Day
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Afegostat Tartrate 150 mg Once Every Four Days
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Afegostat Tartrate 150 mg Once Every Seven Days
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Afegostat Tartrate 25 mg Once Per Day
n=7 participants at risk
Afegostat tartrate was administered orally during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Per Day
n=7 participants at risk
Afegostat tartrate was administered orally once per day during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Every Four Days
n=9 participants at risk
Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period.
|
Afegostat Tartrate 150 mg Once Every Seven Days
n=7 participants at risk
Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period.
|
|---|---|---|---|---|
|
Eye disorders
Dry eye
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Eye disorders
Lacrimation increased
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Gastrointestinal disorders
Abdominal discomfort
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
11.1%
1/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Gastrointestinal disorders
Nausea
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Gastrointestinal disorders
Gingival pain
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
11.1%
1/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
General disorders
Fatigue
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
11.1%
1/9 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
|
Investigations
Alanine aminotransferase increased
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Investigations
Aspartate aminotransferase increased
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Investigations
Platelets counts decreased
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
11.1%
1/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Investigations
Red blood cell count decreased
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
11.1%
1/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
11.1%
1/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Eye disorders
Eyelids pruritus
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Ear and labyrinth disorders
Ear pain
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Gastrointestinal disorders
Abdominal pain
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Infections and infestations
Nasopharyngitis
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Nervous system disorders
Headache
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
11.1%
1/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
11.1%
1/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
General disorders
Pain
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
11.1%
1/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Musculoskeletal and connective tissue disorders
Fasciitis
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
11.1%
1/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Nervous system disorders
Migraine
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
11.1%
1/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
14.3%
1/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
|
General disorders
Sinus headache from seasonal allergies
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
11.1%
1/9 • Day 1 (after dosing) to Day 35
|
0.00%
0/7 • Day 1 (after dosing) to Day 35
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator can publish only the results from this trial, provided they supply the sponsor (or authorized entity) a copy of any proposed publication for review prior to submission for publication. If requested and prior to publication, the investigator will remove information deemed confidential or proprietary by the sponsor and will withhold publication for an additional period of time to allow the sponsor to take appropriate measures to establish and preserve its proprietary rights.
- Publication restrictions are in place
Restriction type: OTHER