Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as revefenacin
TD-4208 · 12 trials · 7 indications
Change from Baseline (Day 1, pre-dose) trough FEV1 on Day 85
Sensitivity analysis results of change from baseline in trough FEV1 (mL) on Day 85 with missing data imputed by last observation carried forward
An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE is an AE that occurred after the participant has received the study drug.
A serious adverse event (SAE) was defined as any untoward medical occurrence occurring at any dose that resulted in any of the following outcomes: * Death * Life-threatening situation. "Life-threatening" refers to a situation in which the participant was at risk of death at the time of the event; it does not refer to an event which might have caused death if it were more severe * Inpatient hospitalization or prolongation of existing hospitalization * Congenital anomaly in the offspring of a participant who received study drug * Important medical events that may not result in death, be immediately life-threatening, or require hospitalization, could have been considered an SAE when, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed in this definition A treatment-emergent SAE is an SAE that occurred after the participant has received the study drug.
Clinically significant changes identified based on change from baseline. Vital signs measured included heart rate, systolic blood pressure and diastolic blood pressure.
Clinically relevant changes identified based on change from baseline. Laboratory Measures assessed included hematology and serum.
Clinically relevant changes identified based on change from baseline.
FEV1 = forced expiratory volume at one second
To assess the safety and tolerability of TD-4208 by assessing the frequency and severity of Treatment Emergent Adverse Events (TEAE)
Weighted mean (0-24hr) Change from baseline FEV1 (forced expiratory volume in 1 second). Measurement is change from baseline.
TD-4208 Cmax derived from plasma concentration-time curves
| Arm | Type | Description |
|---|---|---|
| Revefenacin inhalation solution 175 mcg QD. | EXPERIMENTAL | Revefenacin inhalation solution 175 mcg QD. |
| Placebo inhalation solution QD. | PLACEBO_COMPARATOR | Placebo inhalation solution QD. |
| Period 1: Revefenacin + Formoterol (Sequential) | EXPERIMENTAL | Days 1 to 21: Revefenacin and formoterol will be sequentially administered in the morning. Formoterol will be administered again in the evening. |
| Period 2: Revefenacin + Formoterol (Combo Solution) | EXPERIMENTAL | Days 22 to 42: After a 21 day period, the participants from the Revefenacin + Formoterol (Sequential) Arm will be dosed for 21 days with a combination of revefenacin and formoterol administered as a combined solution. Formoterol will be administered again in the evening. |
| Period 1: Placebo + Formoterol (Sequential) | PLACEBO_COMPARATOR | Days 1 to 21: Placebo versions of revefenacin and formoterol will be sequentially administered in the morning. Formoterol will be administered again in the evening. |
| Period 2: Placebo + Formoterol (Combo Solution) | PLACEBO_COMPARATOR | Days 22 to 42: After a 21 day period, the participants from Placebo + Formoterol (Sequential) Arm the will be dosed for 21 days with a combination of placebo revefenacin and formoterol administered as a combined solution. Formoterol will be administered again in the evening. |
| Revefenacin | EXPERIMENTAL | Active Revefenacin and placebo (in place of Spiriva Handihaler®) |
| Spiriva Handihaler® | ACTIVE_COMPARATOR | Active Spiriva Handihaler® and placebo (in place of Revefenacin) |
| TD-4208-1 | ACTIVE_COMPARATOR | 88 mcg |
| TD-4208-2 | ACTIVE_COMPARATOR | 175 mcg |
| Placebo | PLACEBO_COMPARATOR | Placebo |
| Tiotropium | ACTIVE_COMPARATOR | 18 mcg |
| 44 mcg | EXPERIMENTAL | TD-4208 |
| 88 mcg | EXPERIMENTAL | TD-4208 |
| 175 mcg | EXPERIMENTAL | TD-4208 |
| 350 mcg | EXPERIMENTAL | TD-4208 |
| TD-4208 44 mcg twice daily | EXPERIMENTAL | TD-4208 inhalation solution 44 mcg twice daily for 7 days |
| TD-4208 175 mcg once daily | EXPERIMENTAL | TD-4208 inhalation solution 175 mcg once daily, placebo once daily |
| Dose 1 TD-4208 | EXPERIMENTAL | 22 µg |
| Dose 2 TD-4208 | EXPERIMENTAL | 44 µg |
| Dose 3 TD-4208 | EXPERIMENTAL | 88 µg |
| Dose 4 TD-4208 | EXPERIMENTAL | 175 µg |
| Dose 5 TD-4208 | EXPERIMENTAL | 350 µg |
| Dose 6 TD-4208 | EXPERIMENTAL | 700 µg |
| Renal Impairment | EXPERIMENTAL | Eight subjects with Severe Renal Impairment (eGFR \<30 mL/min/1.73m2). Intervention is TD-4208, 175mcg, inhaled, single dose. |
| Normal Renal Function | EXPERIMENTAL | Eight healthy participants matched to participants with severe renal impairment. Intervention is TD-4208, 175mcg, inhaled, single dose. |
| Hepatic Impairment | EXPERIMENTAL | Eight subjects with Moderate Hepatic Impairment (Child-Pugh B). Drug: TD-4208 175mcg, inhaled, single dose. |
| Normal Hepatic Function | EXPERIMENTAL | Eight healthy participants matched to participants with moderate hepatic impairment. Drug: TD-4208 175mcg, inhaled, single dose. |
| Study Population | EXPERIMENTAL | One dose each of treatments A: \[14C\] TD-4208 20 μg IV administered in a fasted state over 30 minutes. B: \[14C\] TD-4208 200 μg oral solution administered in a fasted state. |
| Name | Type | Description |
|---|---|---|
| Revefenacin 175 mcg in 3 ML Inhalation Solution | DRUG | Revefenacin |
| Placebo inhalation solution QD | DRUG | Placebo |
| Revefenacin | DRUG | Revefenacin is administered via a nebulizer. |
| Placebo | DRUG | Placebo version of Revefenacin is administered via a nebulizer. |
| Formoterol | DRUG | Administered sequentially in both revefenacin and placebo arms using a nebulizer. |
| Spiriva Handihaler® | COMBINATION_PRODUCT | Spiriva Handihaler® contains Spiriva (also known as Tiotropium) and is administered via HandiHaler® device. |
| Placebo for Revefenacin | DRUG | Placebo administered as double blind, double dummy via nebulization. |
| Placebo for Spiriva Handihaler® | DRUG | Placebo administered as double blind, double dummy via Spiriva HandiHaler®. |
| TD-4208 | DRUG | - |
| Tiotropium | DRUG | There is not a placebo, there is an active comparator (Tiotropium) arm. |
Inclusion Criteria: * Key inclusion criteria include: * Males and females of Chinese ethnicity, at least 40 years of age. Females may be of either childbearing or non-childbearing potential. All females of childbearing potential must be using an acceptable, highly effective method of contracepti...
TD-4208 is an investigational small molecule developed by Viatris Inc. (ticker VTRS) for respiratory conditions, primarily chronic obstructive pulmonary disease (COPD). It has also been studied in people with hepatic impairment and renal impairment. TD-4208 is given as an inhaled formulation, referenced in some studies as TD-4208 175 mcg.
TD-4208 is being developed for chronic obstructive pulmonary disease, or COPD. Clinical studies have evaluated it in adults with COPD, including a 52-week safety study and a pharmacokinetic study in healthy male subjects. It is investigational and has not been approved for any use.
TD-4208 is developed by Viatris Inc., which trades under the ticker VTRS. Viatris is the sponsor of the clinical program evaluating TD-4208 across COPD, hepatic impairment, and renal impairment studies.
TD-4208 is in Phase 2 development overall, with completed Phase 1 and Phase 3 studies in its program. It is investigational and not FDA approved. The program includes five completed trials with a total enrollment of 2,363 participants, and no trials are currently active.
Completed TD-4208 trials include NCT02772159, an ADME study in healthy male subjects; NCT02581592, a pharmacokinetics study in moderate hepatic impairment; NCT02578082, a pharmacokinetics study in severe renal impairment; and NCT02518139, a 52-week Phase 3 safety study in COPD. All five trials are completed and none are active.