FindTrial
Sign In

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

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Multiple Intravenous Dose Study to Examine the Safety, Tolerability, and Pharmacokinetics of Intravenous TD-8954, a 5-HT4 Receptor Agonist, in Healthy Subjects

Status
Terminated
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01644240
Enrollment
16
Registered
2012-07-19
Start date
2012-09-30
Completion date
2012-12-31
Last updated
2017-08-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gastrointestinal Motility Disorder

Brief summary

This is a single-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics (PK) of repeated IV doses of TD-8954 in healthy adults 18 to 45 years of age and healthy elderly subjects 65 to 85 years old. A healthy elderly subject population is included to evaluate the safety, tolerability, and PK of TD-8954 IV. Pharmacodynamic effects on bowel movements will also be evaluated. Screening for all cohorts will be conducted within 21 days before the first dose.

Interventions

DRUGTD-8954

Intravenous infusion

DRUGPlacebo - saline

Intravenous infusion

Sponsors

Theravance Biopharma
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes

Inclusion criteria

1. For Cohorts 1: adult males and females age 18 to 45 years, inclusive; for Cohorts 2 and 3, adult males and females 65 to 85 years of age, inclusive; for Cohort 4, adult males and females 18 to 45 or 65 to 85 years of age, inclusive. 2. Body mass index (BMI)between 18 to 36 kg/m2, inclusive. 3. Average frequency of ≥ 3 bowel movements per week.

Exclusion criteria

1. Persistent symptoms of functional GI disorder (such as irritable bowel syndrome, functional constipation, functional dyspepsia, or other symptom-based GI disorders unexplained by a pathologically based disorder) during the 6 months prior to screening, including a history of major surgery of the GI tract, excluding cholecystectomy and appendectomy. 2. History or presence of clinically significant respiratory, GI, renal, hepatic, endocrine, hematological, neurological (including chronic headache, current or prior psychiatric disease/condition, stroke), cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, or dermatological disorders. Subjects with mild, chronic, stable disease (e.g., controlled hypertension, controlled hypercholesterolemia, non insulin-dependent diabetes, osteoarthritis) may be enrolled if the condition is well controlled and not anticipated to interfere with the objectives of the study.

Design outcomes

Primary

MeasureTime frameDescription
CLssDay 5Apparent clearance
CmaxDay 1Maximum concentration in plasma following dosing on Day 1
TmaxDay 1Time to maximum plasma concentration
t½Day 1Time to 50% plasma concentration
AUC0-24Day 1Area under the plasma concentration time curve through 24 hours after dosing.
AUC0-∞Day 1Area under the concentration time curve from time 0 to infinity.
AUCtauDay 1Area under the plasma concentration time curve over the dosing interval estimated using the linear trapezoidal rule.
Plasma VzDay 1Volume of distribution
Plasma CLDay 1Plasma clearance
VssDay 5Apparent volume of distribution at steady state

Secondary

MeasureTime frame
Number of Subjects With Adverse Events1 week

Countries

United States

Participant flow

Participants by arm

ArmCount
TD-8954 Dose 1
TD-8954: Intravenous infusion
6
Placebo
Placebo - saline: Intravenous infusion
4
TD-8954 Dose 2
TD-8954: Intravenous infusion
6
Total16

Baseline characteristics

CharacteristicTD-8954 Dose 1PlaceboTD-8954 Dose 2Total
Age, Continuous32.2 years
STANDARD_DEVIATION 4.92
37.0 years
STANDARD_DEVIATION 3.56
30.2 years
STANDARD_DEVIATION 5.98
32.6 years
STANDARD_DEVIATION 5.49
Region of Enrollment
United States
6 Participants4 Participants6 Participants16 Participants
Sex: Female, Male
Female
2 Participants2 Participants3 Participants7 Participants
Sex: Female, Male
Male
4 Participants2 Participants3 Participants9 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
5 / 61 / 42 / 6
serious
Total, serious adverse events
0 / 60 / 40 / 6

Outcome results

Primary

AUC0-∞

Area under the concentration time curve from time 0 to infinity.

Time frame: Day 1

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1AUC0-∞50600 pg*hr/mLStandard Deviation 5440
TD-8954 Dose 2AUC0-∞15300 pg*hr/mL—
Primary

AUC0-∞

Area under the plasma concentration time curve from 0 to infinity.

Time frame: Day 5

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1AUC0-∞80400 pg*hr/mLStandard Deviation 15700
TD-8954 Dose 2AUC0-∞102000 pg*hr/mLStandard Deviation 12300
Primary

AUC0-24

Area under the plasma concentration time curve through 24 hours after dosing.

Time frame: Day 1

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1AUC0-2441500 pg*hr/mLStandard Deviation 2740
TD-8954 Dose 2AUC0-2412800 pg*hr/mL—
Primary

AUC0-24

Area under the plasma concentration time curve 24 hours following the last dose.

Time frame: Day 5

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1AUC0-2451000 pg*hr/mLStandard Deviation 9310
TD-8954 Dose 2AUC0-2463300 pg*hr/mLStandard Deviation 11800
Primary

AUCtau

Area under the plasma concentration time curve over the dosing interval estimated using the linear trapezoidal rule.

Time frame: Day 5

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1AUCtau68700 pg*hr/mLStandard Deviation 12700
TD-8954 Dose 2AUCtau86300 pg*hr/mLStandard Deviation 12800
Primary

AUCtau

Area under the plasma concentration time curve over the dosing interval estimated using the linear trapezoidal rule.

Time frame: Day 1

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1AUCtau37600 pg*hr/mLStandard Deviation 7070
TD-8954 Dose 2AUCtau8180 pg*hr/mLStandard Deviation 2610
Primary

CLss

Apparent clearance

Time frame: Day 5

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1CLss10.1 L/hrStandard Deviation 2
TD-8954 Dose 2CLss8.11 L/hrStandard Deviation 1.34
Primary

Cmax

Maximum plasma concentration

Time frame: Day 5

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1Cmax7070 pg/mLStandard Deviation 1550
TD-8954 Dose 2Cmax7600 pg/mLStandard Deviation 1650
Primary

Cmax

Maximum concentration in plasma following dosing on Day 1

Time frame: Day 1

Population: 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.

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1Cmax6920 pg/mLStandard Deviation 2120
TD-8954 Dose 2Cmax1200 pg/mLStandard Deviation 275
Primary

Plasma CL

Plasma clearance

Time frame: Day 1

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1Plasma CL9.95 L/hrStandard Deviation 1.03
TD-8954 Dose 2Plasma CL6.55 L/hr—
Primary

Plasma Vz

Volume of distribution

Time frame: Day 1

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1Plasma Vz147 LitersStandard Deviation 9.37
TD-8954 Dose 2Plasma Vz82.8 Liters—
Primary

t½

Time to 50% plasma concentration

Time frame: Day 1

Population: Subjects did not meet extrapolation criteria and were not included in the analysis.

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1t½10.3 hoursStandard Deviation 1.22
TD-8954 Dose 2t½8.77 hours—
Primary

t½

Time to 50% plasma concentration

Time frame: Day 5

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1t½18.0 hoursStandard Deviation 3.18
TD-8954 Dose 2t½18.9 hoursStandard Deviation 3.47
Primary

Tmax

Time to maximum plasma concentration

Time frame: Day 1

ArmMeasureValue (MEDIAN)
TD-8954 Dose 1Tmax0.983 hours
TD-8954 Dose 2Tmax0.887 hours
Primary

Tmax

Time to reach maximum plasma concentration.

Time frame: Day 5

ArmMeasureValue (MEDIAN)
TD-8954 Dose 1Tmax0.983 hours
TD-8954 Dose 2Tmax0.983 hours
Primary

Vss

Apparent volume of distribution at steady state

Time frame: Day 5

ArmMeasureValue (MEAN)Dispersion
TD-8954 Dose 1Vss225 LStandard Deviation 68.1
TD-8954 Dose 2Vss194 LStandard Deviation 60.4
Secondary

Number of Subjects With Adverse Events

Time frame: 1 week

ArmMeasureValue (NUMBER)
TD-8954 Dose 1Number of Subjects With Adverse Events5 participants
PlaceboNumber of Subjects With Adverse Events1 participants
TD-8954 Dose 2Number of Subjects With Adverse Events2 participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026