Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Ampreloxetine <Dose A>, TD-9855
Ampreloxetine · 8 trials · 15 indications
Score change from baseline on the composite of Questions 1 - 6 of the Orthostatic Hypotension Symptom Assessment (OHSA).
OHSA is an assessment of the severity of symptoms from low blood pressure. OHSA is a 6 question symptom assessment scale where each question uses an 11 point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference. Question #1 assesses dizziness, lightheadedness, feeling faint, or feeling like you might blackout. A mean negative change from baseline indicates a better outcome.
Placebo referred to the Day 1 visit, and the change from placebo referred to the time-matched difference from each TD-9855 dosing day (Days 2 through 5) relative to placebo dosing (Day 1).
Baseline was defined as the pre-dose measurement on Day 1 of Part B.
The Likert Scale is question 1 of the Orthostatic Hypotension Symptom Assessment (OHSA). The question asks participants to rate the severity of their orthostatic hypotension symptoms (dizziness, lightheadedness, feeling faint, or feeling like you might black out) on an 11-point scale from 0 to 10, with 0 indicating no symptoms/no interference and 10 indicating the worst possible symptoms/complete interference. A higher score indicates a worse outcome. Baseline was defined as the pre-lunch measurement on Day -1.
Pain NRS score is based on an 11-point scale where 0 represents no pain and 10 represents the worst possible pain.
The AISRS is a modified version of the ADHD Rating Scale that more accurately reflects the impact and severity of ADHD among adults. It is a clinician-administered scale that measures all 18 symptoms of adult ADHD using a Likert scale from 0 (not present) to 3 (severe). The total score ranges from 0 to 54 with a negative change from baseline indicating an improvement in severity/reduction in symptoms.
Change in QTcF from baseline
Estimation of Area under the concentration-time curve, from time zero to the last measured time point
Estimation of AUC from time zero extrapolated to infinity
Estimation of maximum observed plasma concentration
Urinary and fecal recovery of total radioactivity. Whole blood and plasma concentrations of total radioactivity.
| Arm | Type | Description |
|---|---|---|
| Ampreloxetine (Open Label) | ACTIVE_COMPARATOR | Participants will receive ampreloxetine as a single, oral, daily dose of active drug for 12 weeks. |
| Ampreloxetine (Randomized Withdrawal) | PLACEBO_COMPARATOR | After completing the open label, participants are randomized to either ampreloxetine or placebo receiving a single, oral, daily dose of active drug or placebo for a further 8 weeks. |
| Long-Term Extension Period | ACTIVE_COMPARATOR | Participants will receive ampreloxetine as a single, oral, daily dose of active drug for 104 weeks. |
| ampreloxetine | EXPERIMENTAL | Participants randomized to ampreloxetine will receive a single, oral, daily dose of active drug for 4 weeks. |
| Placebo | PLACEBO_COMPARATOR | Participants randomized to Placebo will receive a single, oral, daily dose of placebo for 4 weeks. |
| TD-9855 Part A | EXPERIMENTAL | Subjects will receive placebo and escalating single doses of TD-9855 |
| TD-9855 Part B | EXPERIMENTAL | Subjects will receive a single dose of TD-9855 or placebo. |
| TD-9855 Part C | EXPERIMENTAL | Subjects will receive once daily doses of TD-9855 for up to 5 months as part of an optional outpatient open-label extension arm. |
| TD-9855 Group 1 | EXPERIMENTAL | Group 1 to be dosed with TD-9855 |
| TD-9855 Group 2 | EXPERIMENTAL | Group 2 to be dosed with TD-9855 |
| TD-9855 Dose 1 | EXPERIMENTAL | - |
| TD-9855 Dose 2 | EXPERIMENTAL | - |
| Group 1a | ACTIVE_COMPARATOR | Day 1: Single dose of Moxifloxacin Placebo; Day 1 - Day 15: Single daily dose of Ampreloxetine Placebo; Day 15: Single dose of Moxifloxacin \<Dose A\> |
| Group 1b | ACTIVE_COMPARATOR | Day 1: Single dose of Moxifloxacin \<Dose A\>; Day 1 - Day 15: Single daily dose of Ampreloxetine Placebo; Day 15: Single dose of Moxifloxacin Placebo |
| Group 2 - Treatment | EXPERIMENTAL | Day 1: Single dose of Moxifloxacin Placebo; Day 1 - Day 7: Single daily dose of Ampreloxetine \<Dose A\>; Day 8 - Day 14: Single daily dose of Ampreloxetine \<Dose B\>; Day 15: Single dose of Moxifloxacin Placebo; Day 15: Single dose of Ampreloxetine Placebo; |
| Normal Hepatic Function | EXPERIMENTAL | Ampreloxetine Dose A single dose administration to subjects with normal hepatic function |
| Mild Hepatic Function | EXPERIMENTAL | Ampreloxetine Dose A single dose administration to subjects with mild hepatic impairment |
| Moderate Hepatic Function | EXPERIMENTAL | Ampreloxetine Dose A single dose administration to subjects with moderate hepatic impairment |
| Severe Hepatic Function | EXPERIMENTAL | Ampreloxetine Dose A single dose administration to subjects with severe hepatic impairment |
| TD-9855 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Ampreloxetine | DRUG | Oral tablet, QD |
| Placebo | DRUG | Oral tablet, QD |
| TD-9855 | DRUG | Administered orally. |
| TD-9855 Group 1 | DRUG | - |
| TD-9855 Group 2 | DRUG | - |
| Ampreloxetine <Dose A> | DRUG | Ampreloxetine \<Dose A\> will be administered as 1 tablet of \<Dose A\> and 3 tablets of Ampreloxetine Placebo. |
| Ampreloxetine <Dose B> | DRUG | Ampreloxetine \<Dose B\> will be administered as 4 tablets of \<Dose A\> |
| Ampreloxetine Placebo | DRUG | Ampreloxetine Placebo will be administered as 4 tablets of placebo. The placebo tablet will match (in appearance) the ampreloxetine \<Dose A\> tablet. |
| Moxifloxacin | DRUG | Moxifloxacin will be administered orally as a single tablet. |
| Moxifloxacin Placebo | DRUG | Moxifloxacin placebo will be administered orally as a single tablet. The placebo tablet will match (in appearance) the moxifloxacin tablet. |
Inclusion Criteria: * Participant is male or female and at least 30 years old. * Participant has a diagnosis of possible or probable MSA of the Parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C) according to The Gilman Criteria (2008). * Participant has a diagnosis of possible or probable M...
Ampreloxetine is being developed for the treatment of symptomatic neurogenic orthostatic hypotension (nOH), a condition in which blood pressure drops upon standing due to autonomic nervous system failure. It is also being studied in patients with multiple system atrophy who have symptomatic nOH.
Ampreloxetine is a small molecule inhibitor of SLC6A2, the norepinephrine transporter. By inhibiting this transporter, it is designed to increase norepinephrine levels, which can help constrict blood vessels and raise blood pressure when standing, addressing the symptoms of neurogenic orthostatic hypotension.
Ampreloxetine is being developed by Theravance Biopharma, Inc., which trades on the Nasdaq under the ticker TBPH. The company is responsible for the clinical development program of this investigational therapy.
Ampreloxetine is in Phase 1 development according to the overall program status, but it has also been evaluated in Phase 3 trials. It is an investigational drug and has not been approved by the FDA for any indication.
Ampreloxetine has been studied in several clinical trials, including NCT05696717, an active Phase 3 trial in patients with multiple system atrophy and symptomatic nOH; NCT04688632, a completed Phase 1 thorough QT study; NCT04200573, a completed Phase 1 hepatic impairment study; and NCT03750552, a completed Phase 3 trial in primary autonomic failure.
Yes, Ampreloxetine <Dose A> is an alternative name for ampreloxetine. Both names refer to the same investigational drug candidate being developed by Theravance Biopharma for symptomatic neurogenic orthostatic hypotension.