Trial Outcomes & Findings for A Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of a Single Dose of Intravenous TD-8954 Compared With Metoclopramide in Critically Ill Patients With Enteral Feeding Intolerance (NCT NCT01953081)

NCT ID: NCT01953081

Last Updated: 2020-02-18

Results Overview

the number of subjects reporting adverse events by treatment group

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 13 participants
• Primary outcome timeframe: 6 Days
• Results posted on: 2020-02-18

Participant Flow

Participant milestones

Measure	TD-8954 TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours	Metoclopramide Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
Overall Study STARTED	7	6
Overall Study COMPLETED	5	3
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of a Single Dose of Intravenous TD-8954 Compared With Metoclopramide in Critically Ill Patients With Enteral Feeding Intolerance

Baseline characteristics by cohort

Measure	TD-8954 n=7 Participants TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours	Metoclopramide n=6 Participants Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline	Total n=13 Participants Total of all reporting groups
Age, Continuous	54.0 years STANDARD_DEVIATION 25.29 • n=5 Participants	55.5 years STANDARD_DEVIATION 13.37 • n=7 Participants	54.7 years STANDARD_DEVIATION 19.9 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Australia	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 Days

Population: Safety Population

the number of subjects reporting adverse events by treatment group

Outcome measures

Measure	TD-8954 n=7 Participants TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours	Metoclopramide n=6 Participants Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
Adverse Events	5 participants	4 participants

PRIMARY outcome

Timeframe: 180 minutes

Population: ITT

Number of subjects with retention less than 13% at 180 minutes after dosing.

Outcome measures

Measure	TD-8954 n=7 Participants TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours	Metoclopramide n=6 Participants Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
Gastric Retention by Scintigraphy	6 participants	3 participants

SECONDARY outcome

Timeframe: 72 hours

Population: PK Analysis set for subjects receiving TD-8954, metoclopramide concentrations were not measured in the metoclopramide group.

Time to maximal concentration in plasma

Outcome measures

Measure	TD-8954 n=6 Participants TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours	Metoclopramide Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
Tmax	0.500 hours Interval 0.5 to 1.0	—

SECONDARY outcome

Timeframe: 72 hours

Population: One subject did not receive the full dose of TD-8954 and was excluded from PK analysis for the TD-8954 group; Metoclopramide concentrations were not measured in the Metoclopramide group.

Area under the plasma concentration time curve from 0 to 72 hours after dosing.

Outcome measures

Measure	TD-8954 n=6 Participants TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours	Metoclopramide Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
AUC	23200 pg*hr/mL Standard Deviation 9240	—

SECONDARY outcome

Timeframe: 72 hours

Population: One subject did not receive the full dose of TD-8954 and was excluded from PK analysis for the TD-8954 group; Metoclopramide concentrations were not measured in the Metoclopramide group.

Maximum plasma concentration

Outcome measures

Measure	TD-8954 n=6 Participants TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours	Metoclopramide Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
Cmax	5040 pg/mL Standard Deviation 1780	—

SECONDARY outcome

Timeframe: 180 minutes

Population: One subject in the TD-8954 group did not receive the full dose of TD-8954 and was excluded from the TD-8954 analysis.

Time to 1/2 gastric emptying by breath test

Outcome measures

Measure	TD-8954 n=6 Participants TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours	Metoclopramide n=6 Participants Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
Gastric Emptying by Breath Test	135.7 minutes Standard Deviation 41.61	132.5 minutes Standard Deviation 53.87

SECONDARY outcome

Timeframe: 60 minutes

Population: ITT

Mean gastric retention percentage after dosing.

Outcome measures

Measure	TD-8954 n=7 Participants TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours	Metoclopramide n=8 Participants Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
Percentage Gastric Retention by Scintigraphy at 60 Minutes Postdose	29.6 percentage of retention Standard Deviation 36.28	43.3 percentage of retention Standard Deviation 30.14

SECONDARY outcome

Timeframe: 120 minutes

Population: ITT

Mean gastric retention percentage after dosing.

Outcome measures

Measure	TD-8954 n=7 Participants TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours	Metoclopramide n=8 Participants Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
Percentage Gastric Retention by Scintigraphy at 120 Minutes Postdose	19.6 percentage of retention Standard Deviation 36.10	32.3 percentage of retention Standard Deviation 28.32

SECONDARY outcome

Timeframe: 240 minutes

Population: ITT

Mean gastric retention percentage after dosing.

Outcome measures

Measure	TD-8954 n=7 Participants TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours	Metoclopramide n=8 Participants Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline
Percentage of Gastric Retention by Scintigraphy at 240 Minutes Postdose	11.1 percentage of retention Standard Deviation 24.85	16.3 percentage of retention Standard Deviation 25.64

Adverse Events

TD-8954

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Metoclopramide

Serious events: 3 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	TD-8954 n=7 participants at risk TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours TD-8954	Metoclopramide n=6 participants at risk Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline Metoclopramide
Nervous system disorders Cerebral Hemorrhage	14.3% 1/7 • Number of events 1 • 6 Days	0.00% 0/6 • 6 Days
Nervous system disorders Hemorrhage intracranial	0.00% 0/7 • 6 Days	16.7% 1/6 • Number of events 1 • 6 Days
Nervous system disorders Subarachnoid hemorrhage	0.00% 0/7 • 6 Days	16.7% 1/6 • Number of events 1 • 6 Days
General disorders Disease progression	0.00% 0/7 • 6 Days	16.7% 1/6 • Number of events 1 • 6 Days
Respiratory, thoracic and mediastinal disorders Respiratory failure	14.3% 1/7 • Number of events 1 • 6 Days	0.00% 0/6 • 6 Days

Other adverse events

Measure	TD-8954 n=7 participants at risk TD-8954 single infusion for 1 hour and 4 injections of saline every 6 hours TD-8954	Metoclopramide n=6 participants at risk Metoclopramide 4 doses every 6 hours for 24 hours and 1 hour infusion of saline Metoclopramide
Psychiatric disorders Agitation	14.3% 1/7 • Number of events 1 • 6 Days	0.00% 0/6 • 6 Days
Gastrointestinal disorders Diarrhea	0.00% 0/7 • 6 Days	16.7% 1/6 • Number of events 1 • 6 Days
Metabolism and nutrition disorders Hyperkalemia	14.3% 1/7 • Number of events 1 • 6 Days	0.00% 0/6 • 6 Days
Vascular disorders Hypertension	0.00% 0/7 • 6 Days	16.7% 1/6 • Number of events 1 • 6 Days
Infections and infestations Pneumonia	14.3% 1/7 • Number of events 1 • 6 Days	0.00% 0/6 • 6 Days
Gastrointestinal disorders Vomiting	14.3% 1/7 • Number of events 1 • 6 Days	0.00% 0/6 • 6 Days
Skin and subcutaneous tissue disorders Decubitus ulcer	14.3% 1/7 • Number of events 1 • 6 Days	0.00% 0/6 • 6 Days

Additional Information

Dr. Brett Haumann, SVP, Clinical Development

Theravance Biopharma US, Inc.

Phone: 650-808-6000

Email: BHaumann@theravance.com

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