Table 1.

Trial schedule

		Screening period		Double-blind phase
				Escalation to four tablets/day									Escalation to nine tablets/day							Taper
Timing		Before enrolment	Before start of trial treatment	At start of administration	Week 1	Week 2	Week 3	Week 4	Week 8	Week 12	Week 16	Week 20	Week 21	Week 22	Week 23	Week 24	Week 28	Week 32	Week 36	Week 37
Visit/medical examination		◯	◯	◯	◯	Phone	Phone	◯	◯	◯	◯	◯	◯	Phone	Phone	◯	◯	◯	◯	◯
Informed consent		◯
Neuropsychological/ motor assessment	ADAS-J cog	◯
	SIB-J		◯	◯								◯							◯
	NPI		◯	◯				◯	◯	◯	◯	◯				◯	◯	◯	◯
	MENFIS		◯	◯				◯	◯	◯	◯	◯				◯	◯	◯	◯
	MMSE-J	◯	◯	◯								◯							◯
	DAD		◯	◯								◯							◯
	UPDRS part III		◯	◯								◯							◯
	Apathy Scale		◯	◯								◯							◯
	UMNB		◯	◯								◯							◯
Laboratory biomarkers	Plasma biomarkers		◯	◯						◯		◯					◯		◯
	CSF biomarkers			◯															◯
Digital biomarkers	Wearable physical activity		→	→	→	→	→	→	→	→	→	→	→	→	→	→	→	→	→
	Finger tapping		◯	◯				◯	◯	◯	◯	◯				◯	◯	◯	◯
PET	Brain amyloid PET		◯															◯
	Brain tau PET		◯															◯
Safety assessment	Cardiac ultrasound	◯										◯							◯
	Chest X-ray	◯						◯				◯				◯			◯
	ECG	◯			▲			◯	▲	▲	▲	◯	▲			◯	▲	▲	◯	▲
	Head MRI	◯																	◯
	Blood bromocriptine concentration			◯ *						◯	◯	◯					◯	◯	◯
	Laboratory tests	◯						◯				◯				◯			◯
	AEs		→	→	→	→	→	→	→	→	→	→	→	→	→	→	→	→	→	→

		Extension phase
		Escalation to 4–9 tablets/day†										End of trial
Timing		Week 37	Week 38	Week 39	Week 40	Week 41	Week 42	Week 43	Week 44	Week 45	Week 48	Week 50
Visit/medical examination		◯	Phone	Phone	◯	Phone	Phone	Phone	◯	Phone	◯	◯
Informed consent
Neuropsychological/ motor assessment	ADAS-J cog
	SIB-J
	NPI
	MENFIS
	MMSE-J
	DAD
	UPDRS part III
	Apathy scale
	UMNB
Laboratory biomarkers	Plasma biomarkers
	CSF biomarkers
Digital biomarkers	Wearable physical activity
	Finger tapping
PET	Brain amyloid PET
	Brain tau PET
Safety assessment	Cardiac ultrasound											◯
	Chest X-ray											◯
	ECG	▲			▲				▲		▲	◯
	Head MRI
	Blood bromocriptine concentration
	Laboratory tests				◯							◯
	AEs	→	→	→	→	→	→	→	→	→	→	→

Time after first administration of trial drug (hour)	Before administration	1	2	3	4	6
Time window (in principle)	−2 hours	±5 min	±5 min	±5 min	±5 min	±5 min
Plasma bromocriptine	◯	◯	◯	◯	◯	◯

◯ To be performed.

▲ To be performed if donepezil hydrochloride is coadministered.

· After the final visit of the last participant at week 37, the blind will be broken following data lock to start analyses.

*Schedule for measuring blood bromocriptine concentration on day 1 on the bottom of Table 1.

†Standard dose is four tablets/day, up to nine tablets/day at maximum.

ADAS-J cog, Alzheimer’s Disease Assessment Scale-Cognitive Subscale Japanese Version; AEs, adverse events; CSF, cerebrospinal fluid; DAD, disability assessment for dementia; MENFIS, Mental Function Impairment Scale; MMSE-J, Mini Mental State Examination-Japanese; NPI, Neuro Psychiatric Inventory; PET, positron emission tomography; SIB-J, severe Impairment Battery-Japanese; UMNB, Upper Motor Neuron Burden Score; UPDRS part III, movement disorder society-sponsored revision of the Unified Parkinson’s Disease Rating Scale part III.