Natural Product · PDC-1421

PDC-1421

Phase 2ABVC BioPharma, Inc. (ABVC)

PDC-1421 is a botanical investigational drug whose active ingredient is an extract of Radix Polygalae (the root of Polygala tenuifolia Willd.), given as an oral capsule containing 380 mg of extract. It is developed by BioLite, Inc. (Taiwan), a majority-owned subsidiary of ABVC BioPharma (Nasdaq: ABVC), under the product codes ABV-1504 (major depressive disorder), ABV-1505 (adult ADHD) and ABV-1601 (depression in cancer patients). The company describes it as a botanical norepinephrine reuptake inhibitor, based on in-vitro radioligand-binding assays of the extract run in 2007. It has completed a Phase 1 study in healthy volunteers, a Phase 2 study in major depressive disorder and a two-part Phase 2 program in adult ADHD.

Also known as: PDC-1421, Radix Polygalae extract, PDC 1421, ABV-1504, ABV-1505, ABV-1601, BLI-1005, Polygala tenuifolia extract

Data current as of

Key facts

Modality
Natural product
Mechanism
NET Reuptake inhibitor
Highest phase
Phase 2
Lead indication
Major depressive disorder
Developer
ABVC BioPharma, Inc. (ABVC)
Trials
5 tracked · 1 recruiting · 14 sites
Next catalyst
February 2028 — Registry results (Major depressive disorder)

Mechanism of action#

Mechanism as described by the sponsor: a botanical norepinephrine reuptake inhibitor. In radioligand-binding assays run in 2007, the extract inhibited the norepinephrine transporter with an IC50 of 2.102 micrograms/mL, with weaker activity at the dopamine and serotonin transporters. Because the test article is a multi-component plant extract, this is not a molecular binding constant, and no single active constituent or independent peer-reviewed confirmation of the mechanism was found.

TargetActionAffinity
NETprimarySLC6A2Reuptake inhibitor—ⓘ

Formulations#

FormulationRouteRegimenPharmacokinetics
PDC-1421 oral capsule (380 mg Radix Polygalae extract)
Capsule containing 380 mg PDC-1421 extract. Phase 1: single doses of 1, 3, 6 or 10 capsules (380-3,800 mg) after a meal. Phase 2 MDD and ADHD studies: 1 capsule (low dose, 380 mg) or 2 capsules (high dose, 760 mg) three times daily after meals; 28-day (Part I) to 42-day (MDD Part II) or 56-day (ADHD Part II) treatment periods. Placebo capsules contained corn starch.
OralThree times daily—

Development timeline#

201520202025TodayPhase 113 Nov 2012 — phase change — First subject visit in the Phase 1 single-dose escalation study in healthy volunteers at Taipei Veterans General Hospital (NCT01774045); 30 enrolled, last visit 2013-07-05.Phase 228 Feb 2028 — upcoming — ClinicalTrials.gov estimated primary completion of the Phase I/II PDC-1421 (ABV-1601) study in depression in cancer patients: February 20286 May 2026 — readout (missed) — Phase 2 Part II of PDC-1421 (ABV-1505) in adult ADHD: posted results show no responder advantage over placebo (placebo 50%, low dose 39%, high dose 42%)8 Apr 2024 — phase change — Part II completed (CT.gov study completion date; primary completion 2023-12-06). Results posted 2026-05-06 show no separation from placebo on the primary responder endpoint.8 Apr 2024 — Trial (portion) completed — Phase 2 Part II study of PDC-1421 in adult ADHD completed12 Nov 2023 — Licensing deal — ABVC and BioLite license MDD and ADHD rights for PDC-1421 to AiBtl BioPharma12 Nov 2023 — Licensing deal — ABVC and BioLite license MDD and ADHD rights for PDC-1421 to AiBtl BioPharma7 Apr 2022 — phase change — Randomized, double-blind, placebo-controlled Part II (NCT05202327) started at UCSF and five Taiwanese sites.15 Jul 2020 — phase change — Part I last patient visit; full clinical study report issued 2020-10-24, which the sponsor described as showing safety, tolerability and efficacy.1 Dec 2019 — phase change — Open-label Phase 2 Part I in adult ADHD (NCT02699086, UCSF) started.23 May 2019 — readout (mixed) — Phase 2 PDC-1421 (ABV-1504) in MDD: sponsor reports the high dose met its primary endpoint (MADRS -13.2 vs -9.2 placebo, ITT); the registry-posted Week-6 primary analysis is p=0.39318 Mar 2019 — phase change — Phase 2 MDD study completed (CT.gov study completion date). The sponsor announced results on 2019-05-23, claiming the high dose met its primary endpoint; the registry-posted primary analysis is p=0.393. The 10-Q gives 2019-10-31 as the Phase II completion date.18 Mar 2019 — Trial (portion) completed — Phase 2 study of PDC-1421 in major depressive disorder completed10 Apr 2015 — phase change — Phase 2 MDD study NCT02395978 (BLI-1005-002) started, after US FDA Phase 2 IND clearance in March 2014 and Taiwan FDA clearance in June 2014.
Phase change Readout Event UpcomingHover a marker for details.
Phase 2Apr 2015 – Feb 2028
  1. UpcomingClinicalTrials.gov estimated primary completion of the Phase I/II PDC-1421 (ABV-1601) study in depression in cancer patients: February 2028Major depressive disorder
  2. missedPhase 2 Part II of PDC-1421 (ABV-1505) in adult ADHD: posted results show no responder advantage over placebo (placebo 50%, low dose 39%, high dose 42%)Attention-deficit/hyperactivity disorder
  3. Part II completed (CT.gov study completion date; primary completion 2023-12-06). Results posted 2026-05-06 show no separation from placebo on the primary responder endpoint.Attention-deficit/hyperactivity disorder
  4. Trial (portion) completedPhase 2 Part II study of PDC-1421 in adult ADHD completedAttention-deficit/hyperactivity disorder
  5. Licensing dealABVC and BioLite license MDD and ADHD rights for PDC-1421 to AiBtl BioPharmaMajor depressive disorder↗
  6. Licensing dealABVC and BioLite license MDD and ADHD rights for PDC-1421 to AiBtl BioPharmaAttention-deficit/hyperactivity disorder↗
  7. Randomized, double-blind, placebo-controlled Part II (NCT05202327) started at UCSF and five Taiwanese sites.Attention-deficit/hyperactivity disorder
  8. Part I last patient visit; full clinical study report issued 2020-10-24, which the sponsor described as showing safety, tolerability and efficacy.Attention-deficit/hyperactivity disorder
  9. Open-label Phase 2 Part I in adult ADHD (NCT02699086, UCSF) started.Attention-deficit/hyperactivity disorder
  10. mixedPhase 2 PDC-1421 (ABV-1504) in MDD: sponsor reports the high dose met its primary endpoint (MADRS -13.2 vs -9.2 placebo, ITT); the registry-posted Week-6 primary analysis is p=0.393Major depressive disorder↗
  11. Phase 2 MDD study completed (CT.gov study completion date). The sponsor announced results on 2019-05-23, claiming the high dose met its primary endpoint; the registry-posted primary analysis is p=0.393. The 10-Q gives 2019-10-31 as the Phase II completion date.Major depressive disorder
  12. Trial (portion) completedPhase 2 study of PDC-1421 in major depressive disorder completedMajor depressive disorder
  13. Phase 2 MDD study NCT02395978 (BLI-1005-002) started, after US FDA Phase 2 IND clearance in March 2014 and Taiwan FDA clearance in June 2014.Major depressive disorder
Phase 1Nov 2012
  1. First subject visit in the Phase 1 single-dose escalation study in healthy volunteers at Taipei Veterans General Hospital (NCT01774045); 30 enrolled, last visit 2013-07-05.Major depressive disorder↗

PDC-1421 for Major depressive disorder#

Phase 2CompletedMajor depressive disorder indication →

PDC-1421 (ABV-1504), an oral botanical Radix Polygalae extract described by its sponsor as a norepinephrine reuptake inhibitor, for major depressive disorder. A Phase 1 single-dose escalation study in 30 healthy volunteers in Taiwan (2012-2013) found doses up to 3,800 mg safe. The FDA cleared the Phase 2 IND in March 2014. The Phase 2 study (NCT02395978, BLI-1005-002; Stanford and four Taiwanese sites) randomized 60 adults with moderate-to-severe MDD to 380 mg or 760 mg three times daily or placebo for 6 weeks, after a 12-patient open-label Part I. ABVC reported in 2019 that the high dose met the pre-specified primary endpoint, a 13.2-point MADRS reduction vs 9.2 on placebo. However, the primary analysis posted on ClinicalTrials.gov, a three-arm Kruskal-Wallis test, gives p=0.393, and the low dose did not separate from placebo. ABVC lists the program as Phase II completed and says it will use the high dose in Phase III, which it intends to out-license rather than run itself. No Phase 3 trial has been registered. A related Phase I/II study in depression among cancer patients (ABV-1601, NCT03833206, Cedars-Sinai) is registered but not yet recruiting.

Readouts

  • February 2028AnticipatedRegistry resultsNCT03833206

    ClinicalTrials.gov estimated primary completion of the Phase I/II PDC-1421 (ABV-1601) study in depression in cancer patients: February 2028

  • 2019-05-23ReportedFull resultsmixedNCT02395978

    Phase 2 PDC-1421 (ABV-1504) in MDD: sponsor reports the high dose met its primary endpoint (MADRS -13.2 vs -9.2 placebo, ITT); the registry-posted Week-6 primary analysis is p=0.393 ↗

PDC-1421 for Attention-deficit/hyperactivity disorder#

Phase 2CompletedAttention-deficit/hyperactivity disorder indication →

PDC-1421 (ABV-1505), the same Radix Polygalae extract as ABV-1504, for adult ADHD, on the sponsor's rationale that it may raise norepinephrine levels by inhibiting reuptake. The FDA cleared the Phase 2 IND in January 2016. Part I (NCT02699086, UCSF, 2019-2020) was an open-label study in 6 adults, of whom 5 reached a 40% or greater improvement on the ADHD-RS-IV after 8 weeks. Part II (NCT05202327) was a randomized, double-blind, placebo-controlled study at UCSF and five Taiwanese sites, testing 1 or 2 capsules three times daily for 8 weeks; 69 participants started and it completed in April 2024. Results posted on ClinicalTrials.gov in May 2026 show no advantage over placebo on the primary responder endpoint: 50% responded on placebo, 39% on the low dose and 42% on the high dose. ABVC has not publicly announced Part II topline results, and its 2026 filings still list completing Part II as a goal.

Readouts

  • 2026-05-06ReportedRegistry resultsmissedNCT05202327

    Phase 2 Part II of PDC-1421 (ABV-1505) in adult ADHD: posted results show no responder advantage over placebo (placebo 50%, low dose 39%, high dose 42%)

Clinical trials#

NCT03833206ABV-1601-001Phase 1/2Recruitingn=12

A Phase I/II Study of PDC-1421 for Treating Depression in Cancer Patients: Part I Dose Escalation

Started Jan 2027· Primary completion Feb 2028· 1 site across 1 country

United States

NCT05202327BLI-1008-002Phase 2Completedn=99

PDC-1421 Treatment in Adult Patients With ADHD

Started Apr 2022· Primary completion Dec 2023· 6 sites across 2 countries

TaiwanUnited States

missedprimaryParticipants with >=40% improvement in ADHD-RS-IV from baseline up to 8 weeks (randomized, double-blind, placebo-controlled) — Responders: placebo 11/22 (50%), low dose 9/23 (39%), high dose 10/24 (42%) (No statistical analysis posted)

Neither PDC-1421 dose showed a higher responder rate than placebo; both active arms were numerically lower. Secondary: CGI score of 2 or lower in placebo 6/22, low dose 9/23, high dose 9/24. 69 participants started (registered enrollment 99). Results first posted on ClinicalTrials.gov 2026-05-06. The sponsor's filings describe an interim analysis with a clinical study report sent to the FDA but have not publicly characterized the outcome.

NCT02699086BLI-1008-001Phase 2Completedn=6

A Study of PDC-1421 Treatment in Adult Patients With Attention-Deficit Hyperactivity Disorder (ADHD)

Started Dec 2019· Primary completion Jul 2020· 1 site across 1 country

United States

metprimaryParticipants with >=40% improvement in ADHD-RS-IV from baseline up to 8 weeks (open-label, low dose then high dose) — 5 of 6 participants (ITT) achieved >=40% ADHD-RS-IV improvement at Week 8

Open-label, single-arm, 6-patient study at UCSF (no placebo, no statistical test). The sponsor described PDC-1421 as safe, well tolerated and efficacious in this study. Too small and uncontrolled to establish efficacy.

NCT02395978BLI-1005-002Phase 2Completedn=72

A Phase II Study of PDC-1421 Capsule to Evaluate the Safety and Efficacy in Patients With Major Depressive Disorder

Started Apr 2015· Primary completion Mar 2019· 5 sites across 2 countries

TaiwanUnited States

mixedprimaryChange in MADRS total score from baseline to Week 6 vs placebo (Part II) — ITT (n=21/19/20): high dose (2 capsules TID) -13.19 (SD 9.68), low dose (1 capsule + 1 placebo TID) -9.21 (SD 8.32), placebo -9.2 (SD 7.98). Per-protocol (n=15/15/14): -13.4, -10.4, -8.6. (p=0.393 (Kruskal-Wallis across all three arms, as posted on ClinicalTrials.gov))

Mixed. The sponsor states the high dose met the pre-specified primary endpoint, a 13.2-point MADRS reduction vs 9.2 on placebo (ITT, averaged over the 6-week treatment period). The statistical analysis posted to ClinicalTrials.gov for the Week-6 primary measure is a three-arm Kruskal-Wallis test with p=0.393, and the low dose did not separate from placebo. Small study: 60 randomized in Part II, plus 12 in an open-label Part I. No serious adverse events were reported by the sponsor.

NCT01774045Phase 1Completedn=30

A Dose Escalation Phase I Study of PDC-1421 Capsule to Evaluate the Safety in Healthy Volunteers

Started Nov 2012· Primary completion Jul 2013· 1 site across 1 country

Taiwan

metprimaryDose-limiting toxicities (physical exam, ECG, vital signs, laboratory values, C-SSRS) after single oral doses of 1, 3, 6 or 10 capsules (380-3,800 mg) — 0 dose-limiting toxicities in PDC-1421 and placebo groups on every registered primary measure

Single doses up to 3,800 mg were safe and well tolerated in 30 healthy volunteers in Taiwan, with no dose-limiting toxicities and no suicidal ideation or behavior reported.

Sources#

  1. ABVC BioPharma, Inc. Form 10-K for fiscal year 2025 (filed 2026-03-03) — U.S. Securities and Exchange Commission (EDGAR)
  2. ABVC BioPharma, Inc. Form 10-Q for the quarter ended 2026-06-30 (filed 2026-08-12) — U.S. Securities and Exchange Commission (EDGAR)
  3. NCT01774045 - A Dose Escalation Phase I Study of PDC-1421 Capsule to Evaluate the Safety in Healthy Volunteers (results posted) — ClinicalTrials.gov (U.S. National Library of Medicine)
  4. NCT02395978 (BLI-1005-002) - A Phase II Study of PDC-1421 Capsule to Evaluate the Safety and Efficacy in Patients With Major Depressive Disorder (results posted) — ClinicalTrials.gov (U.S. National Library of Medicine)
  5. NCT02699086 (BLI-1008-001) - A Phase II Tolerability and Efficacy Study of PDC-1421 Treatment in Adult Patients With ADHD, Part I (results posted) — ClinicalTrials.gov (U.S. National Library of Medicine)
  6. NCT03833206 (ABV-1601-001) - A Phase I/II Study of PDC-1421 for Treating Depression in Cancer Patients: Part I Dose Escalation — ClinicalTrials.gov (U.S. National Library of Medicine)
  7. NCT05202327 (BLI-1008-002) - A Phase II Tolerability and Efficacy Study of PDC-1421 Treatment in Adult Patients With ADHD, Part II (results posted 2026-05-06) — ClinicalTrials.gov (U.S. National Library of Medicine)