Trial Outcomes & Findings for A Study of Safety and Efficacy of HPN-100 in Subjects With Cirrhosis and Episodic Hepatic Encephalopathy (NCT NCT00999167)
NCT ID: NCT00999167
Last Updated: 2024-07-10
Results Overview
Part A: The rate of AEs and tolerability of 6 mL and 9 mL doses of HPN-100 were considered the primary safety endpoints for Part A. Safety assessments included adverse events, laboratory tests (including ammonia, hematology, coagulation, liver function and serum chemistry parameters), vital signs, physical and neurological examinations, and electrocardiograms.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
189 participants
Primary outcome timeframe
Part A: 28 days
Results posted on
2024-07-10
Participant Flow
Part A enrollment: 01 December 2009 to 24 February 2010 Part B enrollment: 01 June 2010 to 31 October 2011
The study consisted of Part A, an open-label, dose-escalation lead-in to assess HPN-100 safety and PK, followed by Part B, a randomized, placebo controlled study to assess safety and efficacy of HPN-100.
Participant milestones
| Measure |
HPN-100 6 mL and 9 mL
Subjects will undergo a one step dose escalation over 4 weeks. Subjects will initially receive 6 mL HPN-100 BID for 1 week. On Day 7 and following a satisfactory safety assessment of the subject, the dose will be escalated to 9 mL BID for an additional 3 weeks.
|
HPN-100 6 mL
Subjects will receive 6 mL BID HPN-100 for 16 weeks (Part B)
|
Placebo
Subjects will receive 6 mL BID placebo for 16 weeks (Part B)
|
|---|---|---|---|
|
Part A: Open Label Safety run-in
STARTED
|
15
|
0
|
0
|
|
Part A: Open Label Safety run-in
Received 9 mL BID
|
15
|
0
|
0
|
|
Part A: Open Label Safety run-in
COMPLETED
|
8
|
0
|
0
|
|
Part A: Open Label Safety run-in
NOT COMPLETED
|
7
|
0
|
0
|
|
Part B: Randomized, Placebo Controlled
STARTED
|
0
|
90
|
88
|
|
Part B: Randomized, Placebo Controlled
COMPLETED
|
0
|
55
|
67
|
|
Part B: Randomized, Placebo Controlled
NOT COMPLETED
|
0
|
35
|
21
|
Reasons for withdrawal
| Measure |
HPN-100 6 mL and 9 mL
Subjects will undergo a one step dose escalation over 4 weeks. Subjects will initially receive 6 mL HPN-100 BID for 1 week. On Day 7 and following a satisfactory safety assessment of the subject, the dose will be escalated to 9 mL BID for an additional 3 weeks.
|
HPN-100 6 mL
Subjects will receive 6 mL BID HPN-100 for 16 weeks (Part B)
|
Placebo
Subjects will receive 6 mL BID placebo for 16 weeks (Part B)
|
|---|---|---|---|
|
Part A: Open Label Safety run-in
Met protocol defined stopping rule
|
4
|
0
|
0
|
|
Part A: Open Label Safety run-in
Adverse Event
|
3
|
0
|
0
|
|
Part B: Randomized, Placebo Controlled
Met protocol defined stopping rule
|
0
|
19
|
16
|
|
Part B: Randomized, Placebo Controlled
Withdrawal by Subject
|
0
|
7
|
4
|
|
Part B: Randomized, Placebo Controlled
Adverse Event
|
0
|
6
|
1
|
|
Part B: Randomized, Placebo Controlled
Noncompliance
|
0
|
1
|
0
|
|
Part B: Randomized, Placebo Controlled
Physician Decision
|
0
|
1
|
0
|
|
Part B: Randomized, Placebo Controlled
Physician stopped drug
|
0
|
1
|
0
|
Baseline Characteristics
A Study of Safety and Efficacy of HPN-100 in Subjects With Cirrhosis and Episodic Hepatic Encephalopathy
Baseline characteristics by cohort
| Measure |
HPN-100
n=90 Participants
6 mL BID
|
Placebo
n=88 Participants
6 mL BID
|
Total
n=178 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
85 Participants
n=5 Participants
|
78 Participants
n=7 Participants
|
163 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Age, Continuous
|
53.8 years
STANDARD_DEVIATION 8.94 • n=5 Participants
|
55.4 years
STANDARD_DEVIATION 8.85 • n=7 Participants
|
54.6 years
STANDARD_DEVIATION 8.85 • n=5 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
104 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
44 participants
n=5 Participants
|
44 participants
n=7 Participants
|
88 participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
26 participants
n=5 Participants
|
24 participants
n=7 Participants
|
50 participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
20 participants
n=5 Participants
|
20 participants
n=7 Participants
|
40 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Part A: 28 daysPopulation: Safety population
Part A: The rate of AEs and tolerability of 6 mL and 9 mL doses of HPN-100 were considered the primary safety endpoints for Part A. Safety assessments included adverse events, laboratory tests (including ammonia, hematology, coagulation, liver function and serum chemistry parameters), vital signs, physical and neurological examinations, and electrocardiograms.
Outcome measures
| Measure |
HPN-100 BID
n=15 Participants
6 mL or 9 mL BID HPN-100 (Part A)
|
Placebo
6 mL BID
|
|---|---|---|
|
Part A: The Rate of AEs and Tolerability of HPN-100
Any AE
|
11 Subjects
|
—
|
|
Part A: The Rate of AEs and Tolerability of HPN-100
Gastrointestinal disorders
|
9 Subjects
|
—
|
|
Part A: The Rate of AEs and Tolerability of HPN-100
Metabolism and nutrition disorders
|
7 Subjects
|
—
|
|
Part A: The Rate of AEs and Tolerability of HPN-100
Infection and infestations
|
4 Subjects
|
—
|
|
Part A: The Rate of AEs and Tolerability of HPN-100
Nervous system disorders
|
4 Subjects
|
—
|
|
Part A: The Rate of AEs and Tolerability of HPN-100
Blood and lymphatic system disorders
|
2 Subjects
|
—
|
|
Part A: The Rate of AEs and Tolerability of HPN-100
Injury, poisoning and procedural complications
|
2 Subjects
|
—
|
|
Part A: The Rate of AEs and Tolerability of HPN-100
Musculoskeletal and connective tissue disorders
|
2 Subjects
|
—
|
|
Part A: The Rate of AEs and Tolerability of HPN-100
Psychiatric disorders
|
2 Subjects
|
—
|
|
Part A: The Rate of AEs and Tolerability of HPN-100
Any SAE
|
5 Subjects
|
—
|
|
Part A: The Rate of AEs and Tolerability of HPN-100
Death
|
2 Subjects
|
—
|
PRIMARY outcome
Timeframe: Part B: 112 DaysPopulation: Intent to Treat (ITT)
An HE event was defined as occurrences of either a West Haven (WH) Grade ≥2 or a WH Grade 1 and asterixis grade increase of 1 (if baseline WH = 0). The WH criteria are widely used for rating the severity of HE and are summarized below: Grade 1: trivial lack of awareness, euphoria or anxiety, shortened attention span, impaired performance of addition Grade 2: lethargy or apathy, minimal disorientation for time or place, subtle personality change, inappropriate behavior, impaired performance of subtraction Grade 3: somnolence to semi-stupor but responsive to verbal stimuli, confusion, gross disorientation Grade 4: coma (unresponsive to verbal or noxious stimuli) Asterixis was assessed after arm and forearm extension along with wrist dorsiflexion for 30 seconds and assigned a grade according to the following criteria: Grade 1: rare flaps Grade 2: occasional irregular flaps Grade 3: frequent flaps Grade 4: continuous flaps
Outcome measures
| Measure |
HPN-100 BID
n=90 Participants
6 mL or 9 mL BID HPN-100 (Part A)
|
Placebo
n=88 Participants
6 mL BID
|
|---|---|---|
|
Part B: Proportion of Subjects Who Exhibit an HE Episode, Defined as Either of the Following During the Treatment Phase: WH ≥2; WH Grade and Asterixis Grade Increase of 1 Each, if Baseline WH = 0
|
19 participants
|
32 participants
|
SECONDARY outcome
Timeframe: 112 DaysPopulation: Intent to treat (ITT)
Secondary efficacy endpoint. The total number of HE events during the treatment phase for subjects in the placebo and active arms.
Outcome measures
| Measure |
HPN-100 BID
n=90 Participants
6 mL or 9 mL BID HPN-100 (Part A)
|
Placebo
n=88 Participants
6 mL BID
|
|---|---|---|
|
Total Number of HE Events
|
35 HE event
|
57 HE event
|
SECONDARY outcome
Timeframe: 112 DaysPopulation: Intent to treat (ITT)
Secondary efficacy endpoint. The time to the first HE episode during the treatment period was calculated using the Kaplan-Meier method. Subjects who did not experience an HE episode were censored at the time of their last asterixis assessment. Subjects who had no post-randomization data for the primary endpoint were considered to have an HE episode at Day 1.
Outcome measures
| Measure |
HPN-100 BID
n=90 Participants
6 mL or 9 mL BID HPN-100 (Part A)
|
Placebo
n=88 Participants
6 mL BID
|
|---|---|---|
|
Time to Meeting the Primary Endpoint
|
NA Days
Data are based on Kaplan-Meier point estimates. Because of low event rate (21.1%) it is not possible to estimate the median.
|
NA Days
Data are based on Kaplan-Meier point estimates. Because of low event rate (36.4%) it is not possible to estimate the median
|
SECONDARY outcome
Timeframe: Day 56, Final Visit (D112)Population: Intent to treat (ITT)
Changes from Baseline to Day 56 and the Final Visit were compared between treatment groups using an ANCOVA model for the total index RBANS score ). The index score is a sum of the scores for each of the 5 individual domains (immediate memory, visuospatial/constructional, language, attention). The minimum and maximum total index scores are 40 and 160, respectively; a higher score is better.
Outcome measures
| Measure |
HPN-100 BID
n=90 Participants
6 mL or 9 mL BID HPN-100 (Part A)
|
Placebo
n=88 Participants
6 mL BID
|
|---|---|---|
|
Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score
Change from Baseline to D56 (Total Score)
|
-0.5 units on a scale
Standard Error 1.54
|
3.2 units on a scale
Standard Error 1.37
|
|
Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score
Change from Baseline to Final Visit (Total Score)
|
-10.7 units on a scale
Standard Error 2.85
|
-9.7 units on a scale
Standard Error 3.33
|
Adverse Events
Part A: HPN-100
Serious events: 5 serious events
Other events: 11 other events
Deaths: 0 deaths
Part B: HPN-100
Serious events: 20 serious events
Other events: 71 other events
Deaths: 0 deaths
Part B: Placebo
Serious events: 12 serious events
Other events: 67 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part A: HPN-100
n=15 participants at risk
6 mL BID for 7 days followed by 9 mL BID for 21 days, equivalent to approximately 13.2 and 19.8 grams of HPN-100/day, respectively
|
Part B: HPN-100
n=90 participants at risk
6 mL BID, equivalent to approximately 13.2 grams of HPN-100/day
|
Part B: Placebo
n=88 participants at risk
Matching HPN-100 placebo, 6 mL BID
|
|---|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
6.7%
1/15 • Number of events 1 • Part A: 28 days Part B: 112 days
|
4.4%
4/90 • Number of events 4 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Infections and infestations
Urinary tract infections
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
2.2%
2/90 • Number of events 2 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Infections and infestations
Peritonitis bacterial
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
1.1%
1/90 • Number of events 1 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Infections and infestations
Cellulitis
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
1.1%
1/90 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Infections and infestations
Sepsis
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Infections and infestations
Urosepsis
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
1.1%
1/90 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Hepatobiliary disorders
Hepatic failure
|
6.7%
1/15 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
2.3%
2/88 • Number of events 2 • Part A: 28 days Part B: 112 days
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Hepatobiliary disorders
Hepatorenal syndrome
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Hepatobiliary disorders
Liver disorder
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
1.1%
1/90 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
2.3%
2/88 • Number of events 2 • Part A: 28 days Part B: 112 days
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
6.7%
1/15 • Number of events 1 • Part A: 28 days Part B: 112 days
|
2.2%
2/90 • Number of events 2 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
1.1%
1/90 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
6.7%
1/15 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
2.2%
2/90 • Number of events 2 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
2.2%
2/90 • Number of events 2 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
6.7%
1/15 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
2.2%
2/90 • Number of events 2 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Renal and urinary disorders
Renal failure
|
6.7%
1/15 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
2.2%
2/90 • Number of events 2 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
1.1%
1/90 • Number of events 1 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Investigations
Transaminases increased
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
1.1%
1/90 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Nervous system disorders
Syncope
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
1.1%
1/90 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
1.1%
1/88 • Number of events 1 • Part A: 28 days Part B: 112 days
|
|
Cardiac disorders
Postural orthostatic tachycardia syndrome
|
6.7%
1/15 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
1.1%
1/90 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
1.1%
1/90 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Psychiatric disorders
Acute psychosis
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
1.1%
1/90 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Psychiatric disorders
Psychotic disorder
|
6.7%
1/15 • Number of events 1 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
Other adverse events
| Measure |
Part A: HPN-100
n=15 participants at risk
6 mL BID for 7 days followed by 9 mL BID for 21 days, equivalent to approximately 13.2 and 19.8 grams of HPN-100/day, respectively
|
Part B: HPN-100
n=90 participants at risk
6 mL BID, equivalent to approximately 13.2 grams of HPN-100/day
|
Part B: Placebo
n=88 participants at risk
Matching HPN-100 placebo, 6 mL BID
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
13.3%
2/15 • Number of events 2 • Part A: 28 days Part B: 112 days
|
12.2%
11/90 • Number of events 11 • Part A: 28 days Part B: 112 days
|
14.8%
13/88 • Number of events 15 • Part A: 28 days Part B: 112 days
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
3/15 • Number of events 3 • Part A: 28 days Part B: 112 days
|
8.9%
8/90 • Number of events 8 • Part A: 28 days Part B: 112 days
|
10.2%
9/88 • Number of events 9 • Part A: 28 days Part B: 112 days
|
|
Gastrointestinal disorders
abdominal pain
|
13.3%
2/15 • Number of events 2 • Part A: 28 days Part B: 112 days
|
5.6%
5/90 • Number of events 5 • Part A: 28 days Part B: 112 days
|
5.7%
5/88 • Number of events 5 • Part A: 28 days Part B: 112 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
2.2%
2/90 • Number of events 2 • Part A: 28 days Part B: 112 days
|
9.1%
8/88 • Number of events 8 • Part A: 28 days Part B: 112 days
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
4.4%
4/90 • Number of events 4 • Part A: 28 days Part B: 112 days
|
5.7%
5/88 • Number of events 6 • Part A: 28 days Part B: 112 days
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
5.6%
5/90 • Number of events 6 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
General disorders
Oedema peripheral
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
14.4%
13/90 • Number of events 14 • Part A: 28 days Part B: 112 days
|
8.0%
7/88 • Number of events 7 • Part A: 28 days Part B: 112 days
|
|
Gastrointestinal disorders
Fatigue
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
6.7%
6/90 • Number of events 6 • Part A: 28 days Part B: 112 days
|
8.0%
7/88 • Number of events 8 • Part A: 28 days Part B: 112 days
|
|
General disorders
Pyrexia
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
5.6%
5/90 • Number of events 5 • Part A: 28 days Part B: 112 days
|
3.4%
3/88 • Number of events 3 • Part A: 28 days Part B: 112 days
|
|
Investigations
AST increased
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
11.1%
10/90 • Number of events 11 • Part A: 28 days Part B: 112 days
|
5.7%
5/88 • Number of events 5 • Part A: 28 days Part B: 112 days
|
|
Investigations
ALT increased
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
8.9%
8/90 • Number of events 9 • Part A: 28 days Part B: 112 days
|
4.5%
4/88 • Number of events 4 • Part A: 28 days Part B: 112 days
|
|
Investigations
White blood cell count (WBC) decreased
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
5.6%
5/90 • Number of events 5 • Part A: 28 days Part B: 112 days
|
2.3%
2/88 • Number of events 2 • Part A: 28 days Part B: 112 days
|
|
Nervous system disorders
Headache
|
13.3%
2/15 • Number of events 2 • Part A: 28 days Part B: 112 days
|
8.9%
8/90 • Number of events 10 • Part A: 28 days Part B: 112 days
|
5.7%
5/88 • Number of events 5 • Part A: 28 days Part B: 112 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
5.6%
5/90 • Number of events 5 • Part A: 28 days Part B: 112 days
|
3.4%
3/88 • Number of events 3 • Part A: 28 days Part B: 112 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/15 • Part A: 28 days Part B: 112 days
|
5.6%
5/90 • Number of events 6 • Part A: 28 days Part B: 112 days
|
3.4%
3/88 • Number of events 3 • Part A: 28 days Part B: 112 days
|
|
Infections and infestations
Urinary tract infection
|
13.3%
2/15 • Number of events 2 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
20.0%
3/15 • Number of events 3 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
13.3%
2/15 • Number of events 2 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
13.3%
2/15 • Number of events 2 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
13.3%
2/15 • Number of events 2 • Part A: 28 days Part B: 112 days
|
0.00%
0/90 • Part A: 28 days Part B: 112 days
|
0.00%
0/88 • Part A: 28 days Part B: 112 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER