Trial Outcomes & Findings for A Phase 1, Multiple Intravenous Dose Study to Examine Safety, Tolerability, and PK of Intravenous TD-8954, a 5-HT4 Receptor Agonist, in Healthy Subjects (NCT NCT01644240)
NCT ID: NCT01644240
Last Updated: 2017-08-02
Results Overview
Maximum concentration in plasma following dosing on Day 1
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
Day 1
Results posted on
2017-08-02
Participant Flow
Participant milestones
| Measure |
TD-8954 Dose 1
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
4
|
6
|
|
Overall Study
COMPLETED
|
6
|
4
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Phase 1, Multiple Intravenous Dose Study to Examine Safety, Tolerability, and PK of Intravenous TD-8954, a 5-HT4 Receptor Agonist, in Healthy Subjects
Baseline characteristics by cohort
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
n=4 Participants
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=6 Participants
TD-8954: Intravenous infusion
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
32.2 years
STANDARD_DEVIATION 4.92 • n=5 Participants
|
37.0 years
STANDARD_DEVIATION 3.56 • n=7 Participants
|
30.2 years
STANDARD_DEVIATION 5.98 • n=5 Participants
|
32.6 years
STANDARD_DEVIATION 5.49 • n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Day 1Population: Sample size was 6 at all time points with the exception of 0.5 hours for dose 2 where value was considered an outlier and one subject was excluded from the PK analysis resulting in sample size of 5.
Maximum concentration in plasma following dosing on Day 1
Outcome measures
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=5 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
Cmax
|
6920 pg/mL
Standard Deviation 2120
|
—
|
1200 pg/mL
Standard Deviation 275
|
PRIMARY outcome
Timeframe: Day 1Time to maximum plasma concentration
Outcome measures
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=5 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
Tmax
|
0.983 hours
Interval 0.5 to 0.983
|
—
|
0.887 hours
Interval 0.5 to 0.983
|
PRIMARY outcome
Timeframe: Day 1Population: Subjects did not meet extrapolation criteria and were not included in the analysis.
Time to 50% plasma concentration
Outcome measures
| Measure |
TD-8954 Dose 1
n=3 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=1 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
t½
|
10.3 hours
Standard Deviation 1.22
|
—
|
8.77 hours
|
PRIMARY outcome
Timeframe: Day 1Area under the plasma concentration time curve through 24 hours after dosing.
Outcome measures
| Measure |
TD-8954 Dose 1
n=3 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=1 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
AUC0-24
|
41500 pg*hr/mL
Standard Deviation 2740
|
—
|
12800 pg*hr/mL
|
PRIMARY outcome
Timeframe: Day 1Area under the concentration time curve from time 0 to infinity.
Outcome measures
| Measure |
TD-8954 Dose 1
n=3 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=1 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
AUC0-∞
|
50600 pg*hr/mL
Standard Deviation 5440
|
—
|
15300 pg*hr/mL
|
PRIMARY outcome
Timeframe: Day 1Area under the plasma concentration time curve over the dosing interval estimated using the linear trapezoidal rule.
Outcome measures
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=5 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
AUCtau
|
37600 pg*hr/mL
Standard Deviation 7070
|
—
|
8180 pg*hr/mL
Standard Deviation 2610
|
PRIMARY outcome
Timeframe: Day 1Volume of distribution
Outcome measures
| Measure |
TD-8954 Dose 1
n=3 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=1 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
Plasma Vz
|
147 Liters
Standard Deviation 9.37
|
—
|
82.8 Liters
|
PRIMARY outcome
Timeframe: Day 1Plasma clearance
Outcome measures
| Measure |
TD-8954 Dose 1
n=3 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=1 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
Plasma CL
|
9.95 L/hr
Standard Deviation 1.03
|
—
|
6.55 L/hr
|
PRIMARY outcome
Timeframe: Day 5Maximum plasma concentration
Outcome measures
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=6 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
Cmax
|
7070 pg/mL
Standard Deviation 1550
|
—
|
7600 pg/mL
Standard Deviation 1650
|
PRIMARY outcome
Timeframe: Day 5Time to reach maximum plasma concentration.
Outcome measures
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=6 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
Tmax
|
0.983 hours
Interval 0.5 to 1.02
|
—
|
0.983 hours
Interval 0.5 to 0.983
|
PRIMARY outcome
Timeframe: Day 5Time to 50% plasma concentration
Outcome measures
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=6 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
t½
|
18.0 hours
Standard Deviation 3.18
|
—
|
18.9 hours
Standard Deviation 3.47
|
PRIMARY outcome
Timeframe: Day 5Area under the plasma concentration time curve 24 hours following the last dose.
Outcome measures
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=6 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
AUC0-24
|
51000 pg*hr/mL
Standard Deviation 9310
|
—
|
63300 pg*hr/mL
Standard Deviation 11800
|
PRIMARY outcome
Timeframe: Day 5Area under the plasma concentration time curve from 0 to infinity.
Outcome measures
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=6 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
AUC0-∞
|
80400 pg*hr/mL
Standard Deviation 15700
|
—
|
102000 pg*hr/mL
Standard Deviation 12300
|
PRIMARY outcome
Timeframe: Day 5Area under the plasma concentration time curve over the dosing interval estimated using the linear trapezoidal rule.
Outcome measures
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=6 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
AUCtau
|
68700 pg*hr/mL
Standard Deviation 12700
|
—
|
86300 pg*hr/mL
Standard Deviation 12800
|
PRIMARY outcome
Timeframe: Day 5Apparent volume of distribution at steady state
Outcome measures
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=6 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
Vss
|
225 L
Standard Deviation 68.1
|
—
|
194 L
Standard Deviation 60.4
|
PRIMARY outcome
Timeframe: Day 5Apparent clearance
Outcome measures
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=6 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
CLss
|
10.1 L/hr
Standard Deviation 2.00
|
—
|
8.11 L/hr
Standard Deviation 1.34
|
SECONDARY outcome
Timeframe: 1 weekOutcome measures
| Measure |
TD-8954 Dose 1
n=6 Participants
TD-8954: Intravenous infusion
|
Placebo
n=4 Participants
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=6 Participants
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
Number of Subjects With Adverse Events
|
5 participants
|
1 participants
|
2 participants
|
Adverse Events
TD-8954 Dose 1
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
TD-8954 Dose 2
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
TD-8954 Dose 1
n=6 participants at risk
TD-8954: Intravenous infusion
|
Placebo
n=4 participants at risk
Placebo - saline: Intravenous infusion
|
TD-8954 Dose 2
n=6 participants at risk
TD-8954: Intravenous infusion
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
66.7%
4/6 • Number of events 4
|
0.00%
0/4
|
16.7%
1/6 • Number of events 1
|
|
Nervous system disorders
Dizziness Postural
|
33.3%
2/6 • Number of events 2
|
0.00%
0/4
|
16.7%
1/6 • Number of events 1
|
|
Cardiac disorders
Tachycardia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal Pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
General disorders
Infusion Site Extravasation
|
16.7%
1/6 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Investigations
Transaminases Increased
|
16.7%
1/6 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
Additional Information
Dr. Brett Haumann, SVP, Clinical Development
Theravance Biopharma US, Inc.
Phone: 650-808-6000
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The PI may communicate the trial results generated by the PI, but only after the first publication or presentation of the combined study results generated by all participating sites. The Sponsor can then review trial results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The Sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER